Two and three-dimensional morphometric analysis of trabecular bone using X-ray microtomography (μCT)

Energy Technology Data Exchange (ETDEWEB)

Silva, Alessandro Marcio Hakme da; Silva, Orivaldo Lopes da; Silva Junior, Nelson Ferreira da, E-mail: alhakme@sc.usp.br [Universidade de Sao Paulo (EESC/FMRP/IQSC/USP), Sao Carlos, SP (Brazil); Alves, Jose Marcos [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Escola de Engenharia. Departamento de Engenharia Eletrica e Computacao

2014-07-01

Introduction: trabecular bones have a porous microstructure and can be modeled as linear elastic solids, heterogeneous and anisotropic. In the literature, few investigations have compared the two- dimensional (2D) and three-dimensional (3D) morphometric analyses of cancellous bone. Methods: In this investigation eighteen cylindrical samples of cancellous bone (10 mm of diameter and 20 mm of height) were obtained from six bovine head femurs, with similar values for the weight and age, of the same race and gender. The samples were harvested and freeze at - 20 °C before carrying out the micro CT analysis. The CT-Analyzer software was used to measure in three directions (superior-inferior, lateral-medial and anterior-posterior) parameters such as trabecular thickness, trabecular separation, trabecular number and the eigenvalues of the fabric tensor (M). Results: the Comparison of 2D and 3D analyses for the parameters: 2D (plate model) trabecular thickness, trabecular separation and trabecular number were statistically different (p = 0) showing that measurements are not similar to the 3D ones. However, 2D (rod model) trabecular thickness and 3D trabecular thickness measurements presented no significant difference (p = 0.26). The eigenvalues show that the bovine trabecular microstructure has a tendency to transversally isotropic symmetry. Discussion: The method proved to be quite interesting for the characterization of the bone structure through 3D measurements of trabecular bone morphometric parameters in the three possible directions of loading. The results show that x-ray microtomography (μCT) is a technique of great potential for characterization and generating bone quality parameters for the diagnosis of bone metabolism diseases. (author)

3D Architecture of Trabecular Bone in the Pig Mandible and Femur: Inter-Trabecular Angle Distributions.

Science.gov (United States)

Ben-Zvi, Yehonatan; Reznikov, Natalie; Shahar, Ron; Weiner, Steve

2017-09-01

Cancellous bone is an intricate network of interconnected trabeculae, to which analysis of network topology can be applied. The inter-trabecular angle (ITA) analysis - an analysis of network topological parameters and regularity of network-forming nodes, was previously carried out on human proximal femora and showed that trabecular bone follows two main principles: sparsity of the network connectedness (prevalence of nodes with low connectivity in the network) and maximal space spanning (angular offset of connected elements is maximal for their number and approximates the values of geometrically symmetric shapes). These observations suggest that 3D organization of trabecular bone, irrespective of size and shape of individual elements, reflects a tradeoff between minimal metabolic cost of maintenance and maximal network stability under conditions of multidirectional loading. In this study we validate the ITA application using additional 3D structures (cork and 3D-printed metal lattices), analyze the ITA parameters in porcine proximal femora and mandibles and carry out a spatial analysis of the most common node type in the porcine mandibular condyle. The validation shows that the ITA application reliably detects designed or evolved topological parameters. The ITA parameters of porcine trabecular bones are similar to those of human bones. We demonstrate functional adaptation in the pig mandibular condyle by showing that the planar nodes with 3 edges are preferentially aligned in relation to the muscle forces that are applied to the condyle. We conclude that the ITA topological parameters are remarkable conserved, but locally do adapt to applied stresses.

3D Architecture of Trabecular Bone in the Pig Mandible and Femur: Inter-Trabecular Angle Distributions

Directory of Open Access Journals (Sweden)

Yehonatan Ben-Zvi

2017-09-01

Full Text Available Cancellous bone is an intricate network of interconnected trabeculae, to which analysis of network topology can be applied. The inter-trabecular angle (ITA analysis—an analysis of network topological parameters and regularity of network-forming nodes—was previously carried out on human proximal femora and showed that trabecular bone follows two main principles: sparsity of the network connectedness (prevalence of nodes with low connectivity in the network and maximal space spanning (angular offset of connected elements is maximal for their number and approximates the values of geometrically symmetric shapes. These observations suggest that 3D organization of trabecular bone, irrespective of size and shape of individual elements, reflects a tradeoff between minimal metabolic cost of maintenance and maximal network stability under conditions of multidirectional loading. In this study, we validate the ITA application using additional 3D structures (cork and 3D-printed metal lattices, analyze the ITA parameters in porcine proximal femora and mandibles, and carry out a spatial analysis of the most common node type in the porcine mandibular condyle. The validation shows that the ITA application reliably detects designed or evolved topological parameters. The ITA parameters of porcine trabecular bones are similar to those of human bones. We demonstrate functional adaptation in the pig mandibular condyle by showing that the planar nodes with three edges are preferentially aligned in relation to the muscle forces that are applied to the condyle. We conclude that the ITA topological parameters are remarkably conserved, but locally do adapt to applied stresses.

Mucopolysaccharides in the trabecular meshwork

International Nuclear Information System (INIS)

Ohnishi, Yoshitaka; Yamana, Yasuo; Abe, Masahiro

1982-01-01

The localization of 35 S-sulfate and 3 H-glucosamine in the trabecular region of the hamster was studied by light and electron microscopic autoradiography after the intraperitoneal injection. Exposed silver grains of 35 S-sulfate were concentrated in the trabecular meshwork, sclera and cornea, and grains of 35 H-glucosamine were localized in the trabecular region. The radioactivity of both isotopes was observed in the Golgi apparatuses of the endothelial cells and fibroblasts in Schlemm's canal and the trabecular meshwork. Thereafter, the grains were noted over the entire cytoplasm, except for the nucleus, and then were incorporated into the amorphous substance and collagen fibers in the juxtacanalicular connective tissue. These results suggest that endothelial cells in the trabecular region synthesize and secrete the sulfated mucopolysaccharides and hyaluronic acid. (author)

Influence of cortical endplates on ultrasonic properties of trabecular bone

International Nuclear Information System (INIS)

Kim, Yoon Mi; Lee, Kang Il

2015-01-01

The present study investigated the influence of thick cortical endplates on the ultrasonic properties of trabecular bone in a femur with a high fracture risk. Twelve trabecular bone samples were prepared from bovine femurs, and acrylic plates with thicknesses of 1.25, 1.80, and 2.75 mm were manufactured to simulate the cortical endplates using acrylic with a density and a sound speed similar to cortical bone. Although the thickness of the acrylic plates attached to the two sides of the trabecular bone increased, high correlations were observed between the speed of sound and the apparent bone density of the trabecular bone, with Pearson's correlation coefficients of 0.80-0.86. High correlations were also observed between the attenuation coefficient at 0.5 mm and the apparent bone density of the trabecular bone, with Pearson's correlation coefficients of 0.84-0.91. These results suggest that the speed of sound and attenuation coefficient at a specific frequency measured in a femur with relatively thick cortical endplates compared to the calcaneus could be used as indices for predicting the bone mineral density of the femur.

The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

Science.gov (United States)

Tousen, Yuko; Matsumoto, Yu; Matsumoto, Chiho; Nishide, Yoriko; Nagahata, Yuya; Kobayashi, Isao; Ishimi, Yoshiko

2016-07-01

Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone.

Science.gov (United States)

Liu, X Sherry; Sajda, Paul; Saha, Punam K; Wehrli, Felix W; Bevill, Grant; Keaveny, Tony M; Guo, X Edward

2008-02-01

Trabecular plates and rods are important microarchitectural features in determining mechanical properties of trabecular bone. A complete volumetric decomposition of individual trabecular plates and rods was used to assess the orientation and morphology of 71 human trabecular bone samples. The ITS-based morphological analyses better characterize microarchitecture and help predict anisotropic mechanical properties of trabecular bone. Standard morphological analyses of trabecular architecture lack explicit segmentations of individual trabecular plates and rods. In this study, a complete volumetric decomposition technique was developed to segment trabecular bone microstructure into individual plates and rods. Contributions of trabecular type-associated morphological parameters to the anisotropic elastic moduli of trabecular bone were studied. Seventy-one human trabecular bone samples from the femoral neck (FN), tibia, and vertebral body (VB) were imaged using muCT or serial milling. Complete volumetric decomposition was applied to segment trabecular bone microstructure into individual plates and rods. The orientation of each individual trabecula was determined, and the axial bone volume fractions (aBV/TV), axially aligned bone volume fraction along each orthotropic axis, were correlated with the elastic moduli. The microstructural type-associated morphological parameters were derived and compared with standard morphological parameters. Their contributions to the anisotropic elastic moduli, calculated by finite element analysis (FEA), were evaluated and compared. The distribution of trabecular orientation suggested that longitudinal plates and transverse rods dominate at all three anatomic sites. aBV/TV along each axis, in general, showed a better correlation with the axial elastic modulus (r(2) = 0.95 approximately 0.99) compared with BV/TV (r(2) = 0.93 approximately 0.94). The plate-associated morphological parameters generally showed higher correlations with the

Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

2016-09-15

This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice.

Science.gov (United States)

Holgersen, Kristine; Dobie, Ross; Farquharson, Colin; vanʼt Hof, Rob; Ahmed, Syed Faisal; Hansen, Axel Kornerup; Holm, Thomas L

2015-02-01

Osteoporosis and fractures are common complications of inflammatory bowel disease. The pathogenesis is multifactorial and has been partly attributed to intestinal inflammation. The aim of this study was to evaluate bone status and assess the association between bone loss and gut inflammation in an experimental colitis model. Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone microarchitecture of tibia were determined using micro-computed tomography. Moreover, the serum levels of bone formation and bone resorption biomarkers were measured, and inflammatory protein profiling was performed on colons. PAC IL-10 k.o. mice developed severe colitis, characterized by hyperplasia and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P < 0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice, whereas no differences in cortical bone geometry were observed. The trabecular thickness was inversely correlated with serum levels of CTX (r = -0.93, P = 0.006). Moreover, numerous inflammatory mediators, including RANKL and osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o. mice. PAC IL-10 k.o. mice develop bone loss and changed trabecular structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o. model could be a useful experimental model in preclinical research of inflammatory bowel disease-associated bone loss.

Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

Science.gov (United States)

Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

2013-11-01

Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

Biomechanics and Mechanobiology of Trabecular Bone: A Review

Science.gov (United States)

Oftadeh, Ramin; Perez-Viloria, Miguel; Villa-Camacho, Juan C.; Vaziri, Ashkan; Nazarian, Ara

2015-01-01

Trabecular bone is a highly porous, heterogeneous, and anisotropic material which can be found at the epiphyses of long bones and in the vertebral bodies. Studying the mechanical properties of trabecular bone is important, since trabecular bone is the main load bearing bone in vertebral bodies and also transfers the load from joints to the compact bone of the cortex of long bones. This review article highlights the high dependency of the mechanical properties of trabecular bone on species, age, anatomic site, loading direction, and size of the sample under consideration. In recent years, high resolution micro finite element methods have been extensively used to specifically address the mechanical properties of the trabecular bone and provide unique tools to interpret and model the mechanical testing experiments. The aims of the current work are to first review the mechanobiology of trabecular bone and then present classical and new approaches for modeling and analyzing the trabecular bone microstructure and macrostructure and corresponding mechanical properties such as elastic properties and strength. PMID:25412137

Impaired bone formation in Pdia3 deficient mice.

Directory of Open Access Journals (Sweden)

Yun Wang

Full Text Available 1α,25-Dihydroxyvitamin D3 [1α,25(OH2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3 mediates 1α,25(OH2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/- heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/- mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/- mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/- mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/- heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH2D3's actions in regulating skeletal development.

Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis

Science.gov (United States)

Huang, Le; You, Yong-Ke; Zhu, Tracy Y.; Zheng, Li-Zhen; Huang, Xiao-Ru; Chen, Hai-Yong; Yao, Dong; Lan, Hui-Yao; Qin, Ling

2016-06-01

This study aimed to evaluate the validation of the leptin receptor-deficient mice model for secondary osteoporosis associated with type 2 diabetes mellitus (T2DM) at bone micro-architectural level. Thirty three 36-week old male mice were divided into four groups: normal control (db/m) (n = 7), leptin receptor-deficient T2DM (db/db) (n = 8), human C-reactive protein (CRP) transgenic normal control (crp/db/m) (n = 7), and human CRP transgenic T2DM (crp/db/db) (n = 11). Lumber vertebrae (L5) and bilateral lower limbs were scanned by micro-CT to analyze trabecular and cortical bone quality. Right femora were used for three-point bending to analyze the mechanical properties. Trabecular bone quality at L5 was better in db/db or crp/db/db group in terms of bone mineral density (BMD), bone volume fraction, connectivity density, trabecular number and separation (all p  0.05). Maximum loading and energy yield in mechanical test were similar among groups while the elastic modulus in db/db and crp/db/db significantly lower than db/m. The leptin-receptor mice is not a proper model for secondary osteoporosis associated with T2DM.

Identification of trabecular excrescences, novel microanatomical structures, present in bone in osteoarthropathies

Directory of Open Access Journals (Sweden)

AM Taylor

2012-04-01

Full Text Available It is widely held that bone architecture is finely regulated in accordance with homeostatic requirements. Aberrant remodelling (hyperdensification and/or cyst formation in the immediately subchondral region has previously been described in bone underlying cartilage in arthropathies. The present study examined the trabecular architecture of samples of bone, initially in the severe osteoarthropathy of alkaptonuria, but subsequently in osteoarthritis using a combination of light microscopy, 3D scanning electron microscopy and quantitative backscattered electron scanning electron microscopy. We report an extraordinary and previously unrecognised bone phenotype in both disorders, including novel microanatomical structures. The underlying subchondral trabecular bone contained idiosyncratic architecture. Trabecular surfaces had numerous outgrowths that we have termed "trabecular excrescences", of which three distinct types were recognised. The first type arose from incomplete resorption of branching secondary trabeculae arising from the deposition of immature (woven bone in prior marrow space. These were characterised by very deeply scalloped surfaces and rugged edges. The second type had arisen in a similar way but been smoothed over by new bone deposition. The third type, which resembled coarse stucco, probably arises from resting surfaces that had been focally reactivated. These were poorly integrated with the prior trabecular wall. We propose that these distinctive microanatomical structures are indicative of abnormal osteoclast/osteoblast modelling in osteoarthropathies, possibly secondary to altered mechanical loading or other aberrant signalling. Identification of the mechanisms underlying the formation of trabecular excrescences will contribute to a better understanding of the role of aberrant bone remodelling in arthropathies and development of new therapeutic strategies.

Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology

International Nuclear Information System (INIS)

Weber, Michael H.; Sharp, Jonathan C.; Latta, Peter; Sramek, Milos; Hassard, H. Thomas; Orr, F. William

2005-01-01

Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 μm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological 'gold standard' The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure

Trabecular bone deficits among Vietnamese immigrants.

Science.gov (United States)

Melton, L J; Marquez, M A; McCready, L K; Achenbach, S J; Riggs, B L; Amin, S; Khosla, S

2011-05-01

Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Twenty Vietnamese immigrants (age, 44-79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study.

Diacylglycerol lipase a knockout mice demonstrate metabolic and behavioral phenotypes similar to those of cannabinoid receptor 1 knockout mice

Directory of Open Access Journals (Sweden)

David R Powell

2015-06-01

Full Text Available After creating >4650 knockouts (KOs of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1 KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase a or b (Dagla or Daglb, which catalyze biosynthesis of the endocannabinoid (EC 2-Arachidonoylglycerol (2-AG, or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild type (WT littermates; when data from multiple cohorts of adult mice were combined, body fat was 47% and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. In contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride and total cholesterol levels, and after a glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: 1 the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; 2 in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and 3 small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower body weight and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric

The Evaluation of Epiphyseal Plate Histological Changes in Osteopetrotic op/op Mice.

Directory of Open Access Journals (Sweden)

Aligholi Sobhani

2003-09-01

Full Text Available This study was designed for evaluation of epiphyseal plate histological changes of femur bones in osteopetrotic op/op mice.In this study 5 osteopetrotic op/op mice which were purchased from the commercial source were used.The animals were killed by overdose of chloroform and their femur bones were extracted. The bones were fixed in 10% formaldehyde and decalcified by HCl (0.6N, and routine histological processing were performed. The sections were stained by H&E methods and studied by conventional light microscopy. The results showed that, proliferative zone (PZ and especially hypertrophic zone (HZ were much thickened. In the ossification zone, trabecular bones were irregular and atypical osteoblast cells were observed. The osteoclast cells were not attached to trabecular bones. The bone marrow cavity was restricted and bone marrow cells were poor and scattered. Findings of the present investigation are similar to those reported about epiphyseal plate in osteosclerotic (OC mice in which epiphyseal plate especially hypertrophic zone was thickened and chondrocytes were not substituted for osteoblasts in calcified cartilage area. Also, osteoclast cells had been inactive or absent in OC mice. For prevention of other complication due to the epiphyseal plate changes in new borne, suitable and punctually treatment protocols such as prescription of Macrophage Colony Stimulating-Factor (MCS-F could be useful.

Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

DEFF Research Database (Denmark)

Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

2004-01-01

Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

Science.gov (United States)

Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

2017-11-01

Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

Trabecular bone in the calcaneus of runners.

Directory of Open Access Journals (Sweden)

Andrew Best

Full Text Available Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6, rearfoot-striking runners (n = 6, and non-runners (n = 6, all males aged 20-41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system. We obtained high resolution peripheral computed tomography scans of the posterior calcaneus for both runners and non-runners. No statistically significant differences were found between runners and nonrunners or forefoot strikers and rearfoot strikers. Mean trabecular thickness and mineral density were greatest in forefoot runners with strong effect sizes (<0.80. Trabecular thickness was positively correlated with weekly running distance (r2 = 0.417, p<0.05 and years running (r2 = 0.339, p<0.05 and negatively correlated with age at onset of running (r2 = 0.515, p<0.01 Trabecular thickness, mineral density and bone volume ratio of nonrunners were highly correlated with body mass (r2 = 0.824, p<0.05 and nonrunners were significantly heavier than runners (p<0.05. Adjusting for body mass revealed significantly thicker trabeculae in the posterior calcaneus of forefoot strikers, likely an artifact of greater running volume and earlier onset of running in this subgroup; thus, individuals with the greatest summative loading stimulus had, after body mass adjustment, the thickest trabeculae. Further study with larger sample sizes is necessary to elucidate the role of footstrike on calcaneal trabecular structure. To our knowledge, intraspecific body mass correlations with measures of trabecular robusticity have not been reported elsewhere. We hypothesize that early adoption of running and years of sustained moderate volume running stimulate bone modeling in trabeculae of the

Micro-finite-element method to assess elastic properties of trabecular bone at micro- and macroscopic level.

Science.gov (United States)

Rieger, R; Auregan, J C; Hoc, T

2018-03-01

The objective of the present study is to assess the mechanical behavior of trabecular bone based on microCT imaging and micro-finite-element analysis. In this way two methods are detailed: (i) direct determination of macroscopic elastic property of trabecular bone; (ii) inverse approach to assess mechanical properties of trabecular bone tissue. Thirty-five females and seven males (forty-two subjects) mean aged (±SD) 80±11.7 years from hospitals of Assistance publique-Hôpitaux de Paris (AP-HP) diagnosed with osteoporosis following a femoral neck fracture due to a fall from standing were included in this study. Fractured heads were collected during hip replacement surgery. Standardized bone cores were removed from the femoral head's equator by a trephine in a water bath. MicroCT images acquisition and analysis were performed with CTan ® software and bone volume fraction was then determined. Micro-finite-element simulations were per-formed using Abaqus 6.9-2 ® software in order to determine the macroscopic mechanical behaviour of the trabecular bone. After microCT acquisition, a longitudinal compression test was performed and the experimental macroscopic Young's Modulus was extracted. An inverse approach based on the whole trabecular bone's mechanical response and micro-finite-element analysis was performed to determine microscopic mechanical properties of trabecular bone. In the present study, elasticity of the tissue was shown to be similar to that of healthy tissue but with a lower yield stress. Classical histomorphometric analysis form microCT imaging associated with an inverse micro-finite-element method allowed to assess microscopic mechanical trabecular bone parameters. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mucopolysaccharides in the trabecular meshwork. Light and electron microscopic autoradiography

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Yoshitaka; Yamana, Yasuo; Abe, Masahiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

1982-09-01

The localization of /sup 35/S-sulfate and /sup 3/H-glucosamine in the trabecular region of the hamster was studied by light and electron microscopic autoradiography after the intraperitoneal injection. Exposed silver grains of /sup 35/S-sulfate were concentrated in the trabecular meshwork, sclera and cornea, and grains of /sup 35/H-glucosamine were localized in the trabecular region. The radioactivity of both isotopes was observed in the Golgi apparatuses of the endothelial cells and fibroblasts in Schlemm's canal and the trabecular meshwork. Thereafter, the grains were noted over the entire cytoplasm, except for the nucleus, and then were incorporated into the amorphous substance and collagen fibers in the juxtacanalicular connective tissue. These results suggest that endothelial cells in the trabecular region synthesize and secrete the sulfated mucopolysaccharides and hyaluronic acid.

Short-term survival of the trabecular metal cup is similar to that of standard cups used in acetabular revision surgery.

Science.gov (United States)

Mohaddes, Maziar; Rolfson, Ola; Kärrholm, Johan

2015-02-01

The use of trabecular metal (TM) cups in revision surgery has increased worldwide during the last decade. Since the introduction of the TM cup in Sweden in 2006, this design has gradually replaced other uncemented designs used in Sweden. According to data from the Swedish Hip Arthroplasty Register (SHAR) in 2012, one-third of all uncemented first-time cup revisions were performed using a TM cup. We compared the risk of reoperation and re-revision for TM cups and the 2 other most frequently used cup designs in acetabular revisions reported to the SHAR. The hypothesis was that the performance of TM cups is as good as that of established designs in the short term. The study population consisted of 2,384 patients who underwent 2,460 revisions during the period 2006 through 2012. The most commonly used cup designs were the press-fit porous-coated cup (n = 870), the trabecular metal cup (n = 805), and the cemented all-polyethylene cup (n = 785). 54% of the patients were female, and the median age at index revision was 72 (19-95) years. Reoperation was defined as a second surgical intervention, and re-revision-meaning exchange or removal of the cup-was used as endpoint. The mean follow-up time was 3.3 (0-7) years. There were 215 reoperations, 132 of which were re-revisions. The unadjusted and adjusted risk of reoperation or re-revision was not significantly different for the TM cup and the other 2 cup designs. Our data support continued use of TM cups in acetabular revisions. Further follow-up is necessary to determine whether trabecular metal cups can reduce the re-revision rate in the long term, compared to the less costly porous press-fit and cemented designs.

FRACTAL ANALYSIS OF TRABECULAR BONE: A STANDARDISED METHODOLOGY

Directory of Open Access Journals (Sweden)

Ian Parkinson

2011-05-01

Full Text Available A standardised methodology for the fractal analysis of histological sections of trabecular bone has been established. A modified box counting method has been developed for use on a PC based image analyser (Quantimet 500MC, Leica Cambridge. The effect of image analyser settings, magnification, image orientation and threshold levels, was determined. Also, the range of scale over which trabecular bone is effectively fractal was determined and a method formulated to objectively calculate more than one fractal dimension from the modified Richardson plot. The results show that magnification, image orientation and threshold settings have little effect on the estimate of fractal dimension. Trabecular bone has a lower limit below which it is not fractal (λ<25 μm and the upper limit is 4250 μm. There are three distinct fractal dimensions for trabecular bone (sectional fractals, with magnitudes greater than 1.0 and less than 2.0. It has been shown that trabecular bone is effectively fractal over a defined range of scale. Also, within this range, there is more than 1 fractal dimension, describing spatial structural entities. Fractal analysis is a model independent method for describing a complex multifaceted structure, which can be adapted for the study of other biological systems. This may be at the cell, tissue or organ level and compliments conventional histomorphometric and stereological techniques.

Genetic Dissection of Trabecular Bone Structure with Mouse Intersubspecific Consomic Strains

Directory of Open Access Journals (Sweden)

Taro Kataoka

2017-10-01

Full Text Available Trabecular bone structure has an important influence on bone strength, but little is known about its genetic regulation. To elucidate the genetic factor(s regulating trabecular bone structure, we compared the trabecular bone structures of two genetically remote mouse strains, C57BL/6J and Japanese wild mouse-derived MSM/Ms. Phenotyping by X-ray micro-CT revealed that MSM/Ms has structurally more fragile trabecular bone than C57BL/6J. Toward identification of genetic determinants for the difference in fragility of trabecular bone between the two mouse strains, we employed phenotype screening of consomic mouse strains in which each C57BL/6J chromosome is substituted by its counterpart from MSM/Ms. The results showed that many chromosomes affect trabecular bone structure, and that the consomic strain B6-Chr15MSM, carrying MSM/Ms-derived chromosome 15 (Chr15, has the lowest values for the parameters BV/TV, Tb.N, and Conn.D, and the highest values for the parameters Tb.Sp and SMI. Subsequent phenotyping of subconsomic strains for Chr15 mapped four novel trabecular bone structure-related QTL (Tbsq1-4 on mouse Chr15. These results collectively indicate that genetic regulation of trabecular bone structure is highly complex, and that even in the single Chr15, the combined action of the four Tbsqs controls the fragility of trabecular bone. Given that Tbsq4 is syntenic to human Chr 12q12-13.3, where several bone-related SNPs are assigned, further study of Tbsq4 should facilitate our understanding of the genetic regulation of bone formation in humans.

Age variations in the properties of human tibial trabecular bone and cartilage

DEFF Research Database (Denmark)

Ding, Ming

2000-01-01

, such as apparent, apparent ash and collagen densities of human tibial trabecular bone have significant relationships with age. Tissue density and mineral concentration remain constant throughout life. Trabecular bone is tougher in the younger age, i.e. fracture requires more energy. Collagen density was the single......Initiated and motivated by clinical and scientific problems such as age-related bone fracture, prosthetic loosening, bone remodeling, and degenerative bone diseases, much significant research on the properties of trabecular bone has been carried out over the last two decades. This work has mainly...... focused on the central vertebral trabecular bone, while little is known about age-related changes in the properties of human peripheral (tibial) trabecular bone. Knowledge of the properties of peripheral (tibial) trabecular bone is of major importance for the understanding of degenerative diseases...

Trabecular bone structure correlates with hand posture and use in hominoids.

Directory of Open Access Journals (Sweden)

Zewdi J Tsegai

Full Text Available Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan, suspensory (Pongo, Hylobates and Symphalangus and manipulative (Homo taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link

Suppressor of cytokine signaling 2 (Socs2 deletion protects bone health of mice with DSS-induced inflammatory bowel disease

Directory of Open Access Journals (Sweden)

Ross Dobie

2018-01-01

Full Text Available Individuals with inflammatory bowel disease (IBD often present with poor bone health. The development of targeted therapies for this bone loss requires a fuller understanding of the underlying cellular mechanisms. Although bone loss in IBD is multifactorial, the altered sensitivity and secretion of growth hormone (GH and insulin-like growth factor-1 (IGF-1 in IBD is understood to be a critical contributing mechanism. The expression of suppressor of cytokine signaling 2 (SOCS2, a well-established negative regulator of GH signaling, is stimulated by proinflammatory cytokines. Therefore, it is likely that SOCS2 expression represents a critical mediator through which proinflammatory cytokines inhibit GH/IGF-1 signaling and decrease bone quality in IBD. Using the dextran sodium sulfate (DSS model of colitis, we reveal that endogenously elevated GH function in the Socs2−/− mouse protects the skeleton from osteopenia. Micro-computed tomography assessment of DSS-treated wild-type (WT mice revealed a worsened trabecular architecture compared to control mice. Specifically, DSS-treated WT mice had significantly decreased bone volume, trabecular thickness and trabecular number, and a resulting increase in trabecular separation. In comparison, the trabecular bone of Socs2-deficient mice was partially protected from the adverse effects of DSS. The reduction in a number of parameters, including bone volume, was less, and no changes were observed in trabecular thickness or separation. This protected phenotype was unlikely to be a consequence of improved mucosal health in the DSS-treated Socs2−/− mice but rather a result of unregulated GH signaling directly on bone. These studies indicate that the absence of SOCS2 is protective against bone loss typical of IBD. This study also provides an improved understanding of the relative effects of GH/IGF-1 signaling on bone health in experimental colitis, information that is essential before these drugs are

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals.

Science.gov (United States)

Christen, Patrik; Ito, Keita; van Rietbergen, Bert

2015-03-01

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size-invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno-canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size-dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations. © 2015 Anatomical Society.

Particle migration and gap healing around trabecular metal implants

DEFF Research Database (Denmark)

Rahbek, O; Kold, S; Zippor, Berit

2005-01-01

Bone on-growth and peri-implant migration of polyethylene particles were studied in an experimental setting using trabecular metal and solid metal implants. Cylindrical implants of trabecular tantalum metal and solid titanium alloy implants with a glass bead blasted surface were inserted either i...

Trabecular bone in the calcaneus of runners.

Science.gov (United States)

Best, Andrew; Holt, Brigitte; Troy, Karen; Hamill, Joseph

2017-01-01

Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6), rearfoot-striking runners (n = 6), and non-runners (n = 6), all males aged 20-41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system. We obtained high resolution peripheral computed tomography scans of the posterior calcaneus for both runners and non-runners. No statistically significant differences were found between runners and nonrunners or forefoot strikers and rearfoot strikers. Mean trabecular thickness and mineral density were greatest in forefoot runners with strong effect sizes (forefoot strikers, likely an artifact of greater running volume and earlier onset of running in this subgroup; thus, individuals with the greatest summative loading stimulus had, after body mass adjustment, the thickest trabeculae. Further study with larger sample sizes is necessary to elucidate the role of footstrike on calcaneal trabecular structure. To our knowledge, intraspecific body mass correlations with measures of trabecular robusticity have not been reported elsewhere. We hypothesize that early adoption of running and years of sustained moderate volume running stimulate bone modeling in trabeculae of the posterior calcaneus.

Relationships between bone strength and bone quality. Three-dimensional imaging analysis in ovariectomized mice

International Nuclear Information System (INIS)

Wakabayashi, Suguru; Sakurai, Takashi; Kashima, Isamu

2004-01-01

Low-energy trauma resulting in fractures of the distal femur is often observed in elderly patients with osteoporosis; such fractures are often associated with treatment difficulties and poor prognosis. The purpose of this study was to clarify the factors that affect the bone strength of the distal femur. We used ovariectomized mice to demonstrate bone quality factors associated with deterioration of the strength of the distal femur. Ten-week old ICR-strain mice were ovariectomized or sham-ovariectomized. Total bone mineral density (BMD), total bone area, cortical BMD, cortical thickness, and trabecular BMD were measured by peripheral quantitative computed tomography in the distal metaphyseal region of the femora. As three-dimensional architectural parameters, the trabecular number, trabecular thickness (Tb.Th), trabecular separation, and connectivity density were measured in the same region by micro-computed tomography. The maximum load measured by compression testing of the distal metaphyseal region was regarded as the bone strength of each sample. No significant differences in total bone area or in cortical BMD were found between the groups. Bone strength showed the closest relationship with total BMD (r=0.834). Multiple regression analysis demonstrated that total BMD greatly depended on cortical thickness. The addition of Tb.Th to trabecular BMD markedly reflected bone strength (R=0.857), suggesting that Tb.Th affected bone strength more significantly than trabecular BMD. These findings suggested that deterioration of bone strength of the distal femur (metaphysis) was not caused by a reduction in cortical BMD, but was related to reduced cortical thickness, which reduced total BMD, and to trabecular BMD and architecture, in particular to reduced Tb.Th. (author)

Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

Science.gov (United States)

Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

2017-04-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

Anorexia Nervosa: Analysis of Trabecular Texture with CT.

Science.gov (United States)

Tabari, Azadeh; Torriani, Martin; Miller, Karen K; Klibanski, Anne; Kalra, Mannudeep K; Bredella, Miriam A

2017-04-01

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016.

Osteoarthritis alters the patellar bones subchondral trabecular architecture.

Science.gov (United States)

Hoechel, Sebastian; Deyhle, Hans; Toranelli, Mireille; Müller-Gerbl, Magdalena

2017-09-01

Following the principles of "morphology reveals biomechanics," the cartilage-osseous interface and the trabecular network show defined adaptation in response to physiological loading. In the case of a compromised relationship, the ability to support the load diminishes and the onset of osteoarthritis (OA) may arise. To describe and quantify the changes within the subchondral bone plate (SBP) and trabecular architecture, 10 human OA patellae were investigated by CT and micro-CT. The results are presented in comparison to a previously published dataset of 10 non-OA patellae which were evaluated in the same manner. The analyzed OA samples showed no distinctive mineralization pattern in regards to the physiological biomechanics, but a highly irregular disseminated distribution. In addition, no regularity in bone distribution and architecture across the trabecular network was found. We observed a decrease of material as the bone volume and trabecular thickness/number were significantly reduced. In comparison to non-OA samples, greatest differences for all parameters were found within the first mm of trabecular bone. The differences decreased toward the fifth mm in a logarithmic manner. The interpretation of the logarithmic relation leads to the conclusion that the main impact of OA on bony structures is located beneath the SBP and lessens with depth. In addition to the clear difference in material with approximately 12% less bone volume in the first mm in OA patellae, the architectural arrangement is more rod-like and isotropic, accounting for an architectural decrease in stability and support. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1982-1989, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Scanning electron microscopy of the trabecular meshwork: Understanding the pathogenesis of primary angle closure glaucoma

Directory of Open Access Journals (Sweden)

Ramanjit Sihota

2012-01-01

Full Text Available Purpose: To study ultrastructural changes of the trabecular meshwork in acute and chronic primary angle closure glaucoma (PACG and primary open angle glaucoma (POAG eyes by scanning electron microscopy. Materials and Methods: Twenty-one trabecular meshwork surgical specimens from consecutive glaucomatous eyes after a trabeculectomy and five postmortem corneoscleral specimens were fixed immediately in Karnovsky solution. The tissues were washed in 0.1 M phosphate buffer saline, post-fixed in 1% osmium tetraoxide, dehydrated in acetone series (30-100%, dried and mounted. Results: Normal trabecular tissue showed well-defined, thin, cylindrical uveal trabecular beams with many large spaces, overlying flatter corneoscleral beams and numerous smaller spaces. In acute PACG eyes, the trabecular meshwork showed grossly swollen, irregular trabecular endothelial cells with intercellular and occasional basal separation with few spaces. Numerous activated macrophages, leucocytes and amorphous debris were present. Chronic PACG eyes had a few, thickened posterior uveal trabecular beams visible. A homogenous deposit covered the anterior uveal trabeculae and spaces. Converging, fan-shaped trabecular beam configuration corresponded to gonioscopic areas of peripheral anterior synechiae. In POAG eyes, anterior uveal trabecular beams were thin and strap-like, while those posteriorly were wide, with a homogenous deposit covering and bridging intertrabecular spaces, especially posteriorly. Underlying corneoscleral trabecular layers and spaces were visualized in some areas. Conclusions: In acute PACG a marked edema of the endothelium probably contributes for the acute and marked intraocular pressure (IOP elevation. Chronically raised IOP in chronic PACG and POAG probably results, at least in part, from decreased aqueous outflow secondary to widening and fusion of adjacent trabecular beams, together with the homogenous deposit enmeshing trabecular beams and spaces.

Effects of 1.8 GHz radiofrequency field on microstructure and bone metabolism of femur in mice.

Science.gov (United States)

Guo, Ling; Zhang, Jun-Ping; Zhang, Ke-Ying; Wang, Huan-Bo; Wang, Huan; An, Guang-Zhou; Zhou, Yan; Meng, Guo-Lin; Ding, Gui-Rong

2018-04-30

To investigate the effects of 1.8 GHz radiofrequency (RF) field on bone microstructure and metabolism of femur in mice, C57BL/6 mice (male, age 4 weeks) were whole-body exposed or sham exposed to 1.8 GHz RF field. Specific absorption rates of whole body and bone were approximately 2.70 and 1.14 W/kg (6 h/day for 28 days). After exposure, microstructure and morphology of femur were observed by microcomputed tomography (micro-CT), Hematoxylin and Eosin (HE) and Masson staining. Subsequently, bone parameters were calculated directly from the reconstructed images, including structure model index, bone mineral density, trabecular bone volume/total volume, connectivity density, trabecular number, trabecular thickness, and trabecular separation. Biomarkers that reflect bone metabolism, such as serum total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRACP-5b), were determined by biochemical assay methods. Micro-CT and histology results showed that there was no significant change in bone microstructure and the above parameters in RF group, compared with sham group. The activity of serum ALP and BALP increased 29.47% and 16.82%, respectively, in RF group, compared with sham group (P microstructure; however, it might promote metabolic function of osteoblasts in mice. Bioelectromagnetics. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Altered thermogenesis and impaired bone remodeling in Misty mice.

Science.gov (United States)

Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E; Bornstein, Sheila A; Le, Phuong; Kawai, Masanobu; Lotinun, Sutada; Horowitz, Mark C; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2013-09-01

Fat mass may be modulated by the number of brown-like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age-related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a, and less sympathetic innervation compared to wild-type (+/ +)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wild-type. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wild-type and Misty mice with the β-blocker, propranolol. As predicted, propranolol slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of Misty mice without affecting wild-type. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

Science.gov (United States)

Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

Immobilization induced osteopenia is strain specific in mice

Directory of Open Access Journals (Sweden)

Andreas Lodberg

2015-06-01

Full Text Available Immobilization causes rapid and massive bone loss. By comparing Botulinum Toxin A (BTX-induced bone loss in mouse strains with different genetic backgrounds we investigated whether the genetic background had an influence on the severity of the osteopenia. Secondly, we investigated whether BTX had systemic effects on bone. Female mice from four inbred mouse strains (BALB/cJ, C57BL/6 J, DBA/2 J, and C3H/HeN were injected unilaterally with BTX (n = 10/group or unilaterally with saline (n = 10/group. Mice were euthanized after 21 days, and the bone properties evaluated using μCT, DXA, bone histomorphometry, and mechanical testing. BTX resulted in substantially lower trabecular bone volume fraction (BV/TV and trabecular thickness in all mouse strains. The deterioration of BV/TV was significantly greater in C57BL/6 J (−57% and DBA/2 J (−60% than in BALB/cJ (−45% and C3H/HeN (−34% mice. The loss of femoral neck fracture strength was significantly greater in C57BL/6 J (−47% and DBA/2 J (−45% than in C3H (−25% mice and likewise the loss of mid-femoral fracture strength was greater in C57BL/6 J (−17%, DBA/2 J (−12%, and BALB/cJ (−9% than in C3H/HeN (−1% mice, which were unaffected. Using high resolution μCT we found no evidence of a systemic effect on any of the microstructural parameters of the contralateral limb. Likewise, there was no evidence of a systemic effect on the bone strength in any mouse strain. We did, however, find a small systemic effect on aBMD in DBA/2 J and C3H/HeN mice. The present study shows that BTX-induced immobilization causes the greatest loss of cortical and trabecular bone in C57BL/6 J and DBA/2 J mice. A smaller loss of bone microstructure and fracture strength was seen in BALB/cJ mice, while the bone microstructure and fracture strength of C3H/HeN mice were markedly less affected. This indicates that BTX-induced loss of bone is mouse strain dependent. We found only minimal systemic

In Vivo Over-expression of Circulating Dlk1/Pref-1 Protein Using Hydrodynamic-based Gene Transfer Leads to Lower Bone mass With Marked Effects on Trabecular Bone Micro-architecture

DEFF Research Database (Denmark)

Ding, Ming

determined by PIXImus (LunarR) and micro-CT (ScancoR) respectively. We could only localize the plasmid in the liver and no complications were detected due to transgene expression. Serum levels of FA1 in Dlk1 injected mice (Dlk1+mice) was elevated by more than 15 folds compared to control saline injected mice...... and BMD was negatively correlated with the circulating levels of FA1. Micro-CT analysis revealed significantly decreased micro-architectural parameters of trabecular bone in the distal femur and proximal tibia of the Dlk1+mice compared to controls (see table). Naked DNA delivery by hydrodynamic injection...

Selective inbreeding does not increase gut microbiota similarity in BALB/c mice

DEFF Research Database (Denmark)

Pang, Wanyong; Stradiotto, Damiano; Krych, Lukasz

2012-01-01

microbiota. BALB/cCrl mice were, however, found to have a mean heterozygosity of only 0.8% in their genome, and selection of breeders with a high similarity in the gut microbiota for three generations did not change the overall gut microbiota similarity, which was 66% in the P generation and 66%, 64% and 63...

Trabecular meshwork stiffness in glaucoma.

Science.gov (United States)

Wang, Ke; Read, A Thomas; Sulchek, Todd; Ethier, C Ross

2017-05-01

Alterations in stiffness of the trabecular meshwork (TM) may play an important role in primary open-angle glaucoma (POAG), the second leading cause of blindness. Specifically, certain data suggest an association between elevated intraocular pressure (IOP) and increased TM stiffness; however, the underlying link between TM stiffness and IOP remains unclear and requires further study. We here first review the literature on TM stiffness measurements, encompassing various species and based on a number of measurement techniques, including direct approaches such as atomic force microscopy (AFM) and uniaxial tension tests, and indirect methods based on a beam deflection model. We also briefly review the effects of several factors that affect TM stiffness, including lysophospholipids, rho-kinase inhibitors, cytoskeletal disrupting agents, dexamethasone (DEX), transforming growth factor-β 2 (TGF-β 2 ), nitric oxide (NO) and cellular senescence. We then describe a method we have developed for determining TM stiffness measurement in mice using a cryosection/AFM-based approach, and present preliminary data on TM stiffness in C57BL/6J and CBA/J mouse strains. Finally, we investigate the relationship between TM stiffness and outflow facility between these two strains. The method we have developed shows promise for further direct measurements of mouse TM stiffness, which may be of value in understanding mechanistic relations between outflow facility and TM biomechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperfunctioning solid/trabecular follicular carcinoma of the thyroid gland.

Science.gov (United States)

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the (99m)Tc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

Suitability of texture features to assess changes in trabecular bone architecture

DEFF Research Database (Denmark)

Veenland, JF; Grashuis, JL; Weinans, H

2002-01-01

The purpose of this study was to determine the ability of texture features to assess changes in trabecular bone architecture as projected in radiographs. Micro-CT datasets of trabecular bone were processed to simulate different changes in architecture. Radiographs were simulated by projecting the...

Changes of enzyme activities in lens after glaucoma trabecular resection

Directory of Open Access Journals (Sweden)

Jian-Ping Wang

2013-08-01

Full Text Available AIM: To observe the change of lens antioxidant enzyme activity after glaucoma trabecular resection. METHODS: Thirty-two eyes of sixteen New-Zealand rabbits(2.2-2.4kgwere divided into two groups. The left eyes of rabbits underwent standard glaucoma trabecular resection were treatment group, and the normal right eyes served as controls. Transparency of lenses was monitored by a slit-lamp biomicroscopy before and after glaucoma trabecular resection. The morphology of lens cells was observed under the light microscope.The activities of Na+-K+-ATPase,catalase(CAT, glutathion peroxidase(GSH-px, glutathione reductase(GR, superoxide dismutase(SODand content of malondialdehyde(MDAin lenses were detected six months after trabecular resection. RESULTS: Lenses were clear in both treatment group and normal control group during the six months after operation. The morphology and structure of lens cells were normal under the light microscope in both operation group and normal group. The activity of lens cells antioxidant enzyme activity were significantly decreased in operation group compared with control group, Na+-K+-ATPase declined by 20.97%, CAT declined by 16.36%, SOD declined by 4.46%, GR declined by 4.85%, GSH-px declined by 10.02%, and MDA increased by 16.31%. CONCLUSION: Glaucoma trabecular resection can induce the change of Na+-K+-ATPase, CAT, GSH-px, GR, SOD and MDA in lens of rabbit. Glaucoma filtration surgery for the occurrence of cataract development mechanism has important guiding significance.

Humans and mice express similar olfactory preferences.

Directory of Open Access Journals (Sweden)

Nathalie Mandairon

Full Text Available In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

Science.gov (United States)

Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both pbones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

Directory of Open Access Journals (Sweden)

Luca Giovanella

2010-01-01

Full Text Available A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

Agreement between radiographic and photographic trabecular patterns

Energy Technology Data Exchange (ETDEWEB)

Korstjens, C.M.; Geraets, W.G.M.; Stelt, P.F. van der [Dept. of Oral Radiology, Academic Centre for Dentistry, Amsterdam (Netherlands); Spruijt, R.J. [Div. of Psychosocial Research and Epidemiology, Netherlands Cancer Inst., Amsterdam (Netherlands); Mosekilde, L. [Dept. of Cell Biology, Univ. of Aarhus (Denmark)

1998-11-01

Purpose: It has been hypothesized that photographs can facilitate the interpretation of the radiographic characteristics of trabecular bone. The reliability of these photographic and radiographic approaches has been determined, as have various agreements between the two approaches and their correlations with biomechanical characteristics. Material and Methods: Fourteen vertebral bodies were obtained at autopsy from 6 women and 8 men aged 22-76 years. Photographs (n=28) and radiographs (n=28) were taken of midsagittal slices from the third lumbar vertebra. The radiographs and photographs were digitized and the geometric properties of the trabecular architecture were then determined with a digital images analysis technique. Information on the compressive strength and ash density of the vertebral body was also available. Results: The geometric properties of both radiographs and photographs could be measured with a high degree of reliability (Cronbach`s {alpha}>0.85). Agreement between the radiographic and photographic approaches was mediocre as only the radiographic measurements showed insignificant correlations (p<0.05) with the biomechanical characteristics. We suggest that optical phenomena may result in the significant correlations between the photographs and the biomechanical characteristics. Conclusion: For digital image processing, radiography offers a superior description of the architecture of trabecular bone to that offered by photography. (orig.)

Agreement between radiographic and photographic trabecular patterns

International Nuclear Information System (INIS)

Korstjens, C.M.; Geraets, W.G.M.; Stelt, P.F. van der; Spruijt, R.J.; Mosekilde, L.

1998-01-01

Purpose: It has been hypothesized that photographs can facilitate the interpretation of the radiographic characteristics of trabecular bone. The reliability of these photographic and radiographic approaches has been determined, as have various agreements between the two approaches and their correlations with biomechanical characteristics. Material and Methods: Fourteen vertebral bodies were obtained at autopsy from 6 women and 8 men aged 22-76 years. Photographs (n=28) and radiographs (n=28) were taken of midsagittal slices from the third lumbar vertebra. The radiographs and photographs were digitized and the geometric properties of the trabecular architecture were then determined with a digital images analysis technique. Information on the compressive strength and ash density of the vertebral body was also available. Results: The geometric properties of both radiographs and photographs could be measured with a high degree of reliability (Cronbach's α>0.85). Agreement between the radiographic and photographic approaches was mediocre as only the radiographic measurements showed insignificant correlations (p<0.05) with the biomechanical characteristics. We suggest that optical phenomena may result in the significant correlations between the photographs and the biomechanical characteristics. Conclusion: For digital image processing, radiography offers a superior description of the architecture of trabecular bone to that offered by photography. (orig.)

Ultrastructural analysis of the pigment dispersion syndrome in DBA/2J mice.

Science.gov (United States)

Schraermeyer, Mareike; Schnichels, Sven; Julien, Sylvie; Heiduschka, Peter; Bartz-Schmidt, Karl-Ulrich; Schraermeyer, Ulrich

2009-11-01

To characterise ocular pigment abnormalities associated with iris atrophy in DBA/2J mice as a model for human pigment dispersion syndrome. Immunohistochemistry, electron and light microscopy were performed to examine the eyes of DBA/2J mice ranging in age from 2.5 to 18 months old. The focus of our study was the description of the ultrastructural modifications in the irides of DBA/2J mice. The DBA/2J mice presented modifications in the melanosomes in all the pigmented parts of the eye, including the retinal pigment epithelial cells and choroidal melanocytes of the ciliary pigment epithelium. The extracellular matrix of the iris stroma disappeared with ageing. Pigmented cells detached from the iris and migrated into the trabecular meshwork exclusively on the anterior iris surface. These cells were identified as macrophages by immunohistochemistry and electron microscopy. There was no evidence that melanocytes or iris pigment epithelial cells migrated into the trabecular meshwork, but they became more and more depigmented. The aqueous outflow was blocked by pigment-laden cells, but not by cellular debris or melanosomes. No substantial amount of extracellular melanosomes was observed. The morphology of melanosomes is aberrant in all pigment cells in the eyes of DBA/2J mice. We conclude that the disease process begins with the transfer of both immature melanosomes from the iris pigment epithelium (IPE) and melanocytes to macrophages, which subsequently migrate into the trabecular meshwork. Accumulating macrophages cause a blockade of the chamber angle. As the disease progresses, the IPE, melanocytes and iris stroma, including blood vessels, disappear, leading to iris atrophy. It is speculated that the loss of these pigment cells is partly caused by reduction of the iris stroma.

Evaluation of trabecular bone patterns on dental radiographic images: influence of cortical bone

Science.gov (United States)

Amouriq, Yves; Evenou, Pierre; Arlicot, Aurore; Normand, Nicolas; Layrolle, Pierre; Weiss, Pierre; Guédon, Jean-Pierre

2010-03-01

For some authors trabecular bone is highly visible in intraoral radiographs. For other authors, the observed intrabony trabecular pattern is a representation of only the endosteal surface of cortical bone, not of intermedullary striae. The purpose of this preliminary study was to investigate the true anatomical structures that are visible in routine dental radiographs and classically denoted trabecular bone. This is a major point for bone texture analysis on radiographs. Computed radiography (CR) images of dog mandible section in molar region were compared with simulations calculated from high-resolution micro-CT volumes. Calculated simulations were obtained using the Mojette Transform. By digitally editing the CT volume, the simulations were separated into trabecular and cortical components into a region of interest. Different images were compared and correlated, some bone micro-architecture parameters calculated. A high correlation was found between computed radiographs and calculated simulations from micro-CT. The Mojette transform was successful to obtain high quality images. Cortical bone did not contribute to change in a major way simulated images. These first results imply that intrabony trabecular pattern observed on radiographs can not only be a representation of the cortical bone endosteal surface and that trabecular bone is highly visible in intraoral radiographs.

Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound

Science.gov (United States)

Qin, Yi-Xian; Lin, Wei; Mittra, Erik; Xia, Yi; Cheng, Jiqi; Judex, Stefan; Rubin, Clint; Müller, Ralph

2013-11-01

Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone's mechanical strength and structural parameters, i.e., bulk Young's modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young's modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone's structural integrity.

Trabecular bone structure parameters from 3D image processing of clinical multi-slice and cone-beam computed tomography data

Energy Technology Data Exchange (ETDEWEB)

Klintstroem, Eva; Smedby, Oerjan [Linkoeping University, Center for Medical Image Science and Visualization (CMIV), Linkoeping (Sweden); UHL County Council of Oestergoetland, Department of Radiology, Linkoeping (Sweden); Linkoeping University, Department of Medical and Health Sciences (IMH)/Radiology, Linkoeping (Sweden); Moreno, Rodrigo [Linkoeping University, Center for Medical Image Science and Visualization (CMIV), Linkoeping (Sweden); Linkoeping University, Department of Medical and Health Sciences (IMH)/Radiology, Linkoeping (Sweden); Brismar, Torkel B. [KUS Huddinge, Department of Clinical Science, Intervention and Technology at Karolinska Institutet and Department of Radiology, Stockholm (Sweden)

2014-02-15

Bone strength depends on both mineral content and bone structure. The aim of this in vitro study was to develop a method of quantitatively assessing trabecular bone structure by applying three-dimensional image processing to data acquired with multi-slice and cone-beam computed tomography using micro-computed tomography as a reference. Fifteen bone samples from the radius were examined. After segmentation, quantitative measures of bone volume, trabecular thickness, trabecular separation, trabecular number, trabecular nodes, and trabecular termini were obtained. The clinical machines overestimated bone volume and trabecular thickness and underestimated trabecular nodes and number, but cone-beam CT to a lesser extent. Parameters obtained from cone beam CT were strongly correlated with μCT, with correlation coefficients between 0.93 and 0.98 for all parameters except trabecular termini. The high correlation between cone-beam CT and micro-CT suggest the possibility of quantifying and monitoring changes of trabecular bone microarchitecture in vivo using cone beam CT. (orig.)

Vertebral body trabecular density at the thoracolumbar junction using quantitative computed tomography

International Nuclear Information System (INIS)

Singer, K.P.; Breidahl, P.D.; Royal Perth Hospital

1990-01-01

Quantitative computed tomography was used to assess vertebral trabecular density in 26 post-mortem spines from individuals aged between 14 and 80 years. All vertebrae from T10 to L1 were scanned transversely near the mid-vertebral level with calculations of trabecular density in HUs averaged and referenced to a mineral equivalent phantom. An age-related decline in trabecular density was recorded (r=0.55, p<0.0001). Density measures from the anterior aspect of the vertebral body were significantly greater than from postero-lateral regions. From T10 to L1, there was a significant decrease in trabecular density, whereas density measures multiplied by vertebral body cross-sectional area were constant. Predictions of vertebral compressive strength using quantitative computed tomography may become more accurate by increasing the sampling area per scan and including vertebral body cross-sectional area as part of the radiologic assessment. (orig.)

Trabecular mineral content of the spine in women with hip fracture: CT measurement

International Nuclear Information System (INIS)

Firooznia, H.; Rafii, M.; Golimbu, C.; Schwartz, M.S.; Ort, P.

1986-01-01

The trabecular bone mineral content (BMC) of the spine was measured by computed tomography in 185 women aged 47-84 years with vertebral fracture (n = 74), hip fracture (n = 83), and both vertebral and hip fracture (n = 28). Eighty-seven percent of vertebral-fracture patients, 38% of hip-fracture patients, and 82% of vertebral- and hip-fracture patients had spinal BMC values below the fifth percentile for healthy premenopausal women and values 64%, 9%, and 68% below the fifth percentile for age-matched control subjects. No significant loss of spinal trabecular bone was seen in patients with hip fracture. If it is assumed that the rate of trabecular bone loss is the same in the spine and femoral neck, then hip fracture (unlike osteoporotic vertebral fracture) is not associated with disproportionate loss of trabecular bone. Hip fracture occurs secondary to weakening of bone and increased incidence of falls. Bone weakening may be due to disproportionate loss of trabecular or cortical bone, proportionate loss of both, or other as yet undetermined qualitative changes in bone

INAA of cortical and trabecular bone samples from animals

International Nuclear Information System (INIS)

Takata, M.K.; Saiki, M.

2004-01-01

Instrumental neutron activation analysis (INAA) was applied to determine Ba, Br, Ca, Cl, Fe, K, Mg, Mn, Na, P, Sr and Zn in bovine and porcine rib bones. Precise results were obtained in analyses of freeze-dried cortical and trabecular bones separately, and also of whole bone ashes. Cortical tissues presented higher concentrations of Ba, Ca, Mg, Mn, Na, P, Sr and Zn than those obtained in trabecular ones. Comparisons were also made between the results obtained for bovine and porcine rib bones. (author)

Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

Science.gov (United States)

Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

2015-01-01

Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac

Quantitative computed tomography in measurement of vertebral trabecular bone mass

International Nuclear Information System (INIS)

Nilsson, M.; Johnell, O.; Jonsson, K.; Redlund-Johnell, I.

1988-01-01

Measurement of bone mineral concentration (BMC) can be done by several modalities. Quantitative computed tomography (QCT) can be used for measurements at different sites and with different types of bone (trabecular-cortical). This study presents a modified method reducing the influence of fat. Determination of BMC was made from measurements with single-energy computed tomography (CT) of the mean Hounsfield number in the trabecular part of the L1 vertebra. The method takes into account the age-dependent composition of the trabecular part of the vertebra. As the amount of intravertebral fat increases with age, the effective atomic number for these parts decreases. This results in a non-linear calibration curve for single-energy CT. Comparison of BMC values using the non-linear calibration curve or the traditional linear calibration with those obtained with a pixel-by-pixel based electron density calculation method (theoretically better) showed results clearly in favor of the non-linear method. The material consisted of 327 patients aged 6 to 91 years, of whom 197 were considered normal. The normal data show a sharp decrease in trabecular bone after the age of 50 in women. In men a slower decrease was found. The vertebrae were larger in men than in women. (orig.)

Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork

Energy Technology Data Exchange (ETDEWEB)

Izzotti, Alberto, E-mail: izzotti@unige.it [Mutagenesis Unit, IRCCS AOU San Martino – IST, Genova (Italy); Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); La Maestra, Sebastiano; Micale, Rosanna Tindara; Longobardi, Maria Grazia [Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); Saccà, Sergio Claudio [Ophthalmology Unit, IRCCS AOU San Martino-IST, Genova (Italy)

2015-02-15

Highlights: • Glaucoma drug preservatives induce DNA damage in trabecular meshwork cells. • Cellular alteration is related with the occurrence of activation of apoptosis through the intrinsic pathway. • Drug preservatives unable to induce cell damage are ineffective in killing bacteria. • Anti glaucoma drugs should be formulated as single-dose usage devoid of genotoxic preservatives. - Abstract: Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3

Age variations in the properties of human tibial trabecular bone

DEFF Research Database (Denmark)

Ding, Ming; Dalstra, M; Danielsen, CC

1997-01-01

We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate...... strain and failure energy showed maxima at younger ages. These age-related variations (except for failure energy) were non-linear. Tissue density and mineral concentration were constant throughout life, whereas apparent density (the amount of bone) varied with ultimate stress. Collagen density (the...... amount of collagen) varied with failure energy. Collagen concentration was maximal at younger ages but varied little with age. Our results suggest that the decrease in mechanical properties of trabecular bone such as Young's modulus and ultimate stress is mainly a consequence of the loss of trabecular...

A theoretical framework for strain-related trabecular bone maintenance and adaptation.

Science.gov (United States)

Ruimerman, R; Hilbers, P; van Rietbergen, B; Huiskes, R

2005-04-01

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for these mechanisms we have proposed a mathematical theory (Nature 405 (2000) 704). This theory is based on hypothetical osteocyte stimulation of osteoblast bone formation, as an effect of elevated strain in the bone matrix, and a role for microcracks and disuse in promoting osteoclast resorption. Applied in a 2-D Finite Element Analysis model, the theory explained the formation of trabecular patterns. In this article we present a 3-D FEA model based on the same theory and investigated its potential morphological predictability of metabolic reactions to mechanical loads. The computations simulated the development of trabecular morphological details during growth, relative to measurements in growing pigs, reasonably realistic. They confirmed that the proposed mechanisms also inherently lead to optimal stress transfer. Alternative loading directions produced new trabecular orientations. Reduction of load reduced trabecular thickness, connectivity and mass in the simulation, as is seen in disuse osteoporosis. Simulating the effects of estrogen deficiency through increased osteoclast resorption frequencies produced osteoporotic morphologies as well, as seen in post-menopausal osteoporosis. We conclude that the theory provides a suitable computational framework to investigate hypothetical relationships between bone loading and metabolic expressions.

Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents

Energy Technology Data Exchange (ETDEWEB)

Hamed, Elham [University of Illinois at Urbana-Champaign, Department of Mechanical Science and Engineering, 1206 West Green Street, Urbana, IL 61801 (United States); Novitskaya, Ekaterina, E-mail: eevdokim@ucsd.edu [University of California, San Diego, Department of Mechanical and Aerospace Engineering, Materials Science and Engineering Program, 9500 Gilman Dr., La Jolla, CA 92093 (United States); Li, Jun; Jasiuk, Iwona [University of Illinois at Urbana-Champaign, Department of Mechanical Science and Engineering, 1206 West Green Street, Urbana, IL 61801 (United States); McKittrick, Joanna [University of California, San Diego, Department of Mechanical and Aerospace Engineering, Materials Science and Engineering Program, 9500 Gilman Dr., La Jolla, CA 92093 (United States)

2015-09-01

The elastic moduli of trabecular bone were modeled using an analytical multiscale approach. Trabecular bone was represented as a porous nanocomposite material with a hierarchical structure spanning from the collagen–mineral level to the trabecular architecture level. In parallel, compression testing was done on bovine femoral trabecular bone samples in two anatomical directions, parallel to the femoral neck axis and perpendicular to it, and the measured elastic moduli were compared with the corresponding theoretical results. To gain insights on the interaction of collagen and minerals at the nanoscale, bone samples were deproteinized or demineralized. After such processing, the treated samples remained as self-standing structures and were tested in compression. Micro-computed tomography was used to characterize the hierarchical structure of these three bone types and to quantify the amount of bone porosity. The obtained experimental data served as inputs to the multiscale model and guided us to represent bone as an interpenetrating composite material. Good agreement was found between the theory and experiments for the elastic moduli of the untreated, deproteinized, and demineralized trabecular bone. - Highlights: • A multiscale model was used to predict the elastic moduli of trabecular bone. • Samples included demineralized, deproteinized and untreated bone. • The model portrays bone as a porous, interpenetrating two phase composite. • The experimental elastic moduli for trabecular bone fell between theoretical bounds.

Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents

International Nuclear Information System (INIS)

Hamed, Elham; Novitskaya, Ekaterina; Li, Jun; Jasiuk, Iwona; McKittrick, Joanna

2015-01-01

The elastic moduli of trabecular bone were modeled using an analytical multiscale approach. Trabecular bone was represented as a porous nanocomposite material with a hierarchical structure spanning from the collagen–mineral level to the trabecular architecture level. In parallel, compression testing was done on bovine femoral trabecular bone samples in two anatomical directions, parallel to the femoral neck axis and perpendicular to it, and the measured elastic moduli were compared with the corresponding theoretical results. To gain insights on the interaction of collagen and minerals at the nanoscale, bone samples were deproteinized or demineralized. After such processing, the treated samples remained as self-standing structures and were tested in compression. Micro-computed tomography was used to characterize the hierarchical structure of these three bone types and to quantify the amount of bone porosity. The obtained experimental data served as inputs to the multiscale model and guided us to represent bone as an interpenetrating composite material. Good agreement was found between the theory and experiments for the elastic moduli of the untreated, deproteinized, and demineralized trabecular bone. - Highlights: • A multiscale model was used to predict the elastic moduli of trabecular bone. • Samples included demineralized, deproteinized and untreated bone. • The model portrays bone as a porous, interpenetrating two phase composite. • The experimental elastic moduli for trabecular bone fell between theoretical bounds

MR-based trabecular bone microstructure is not altered in subjects with indolent systemic mastocytosis.

Science.gov (United States)

Baum, Thomas; Karampinos, Dimitrios C; Brockow, Knut; Seifert-Klauss, Vanadin; Jungmann, Pia M; Biedermann, Tilo; Rummeny, Ernst J; Bauer, Jan S; Müller, Dirk

2015-01-01

Subjects with indolent systemic mastocytosis (ISM) have an increased risk for osteoporosis. It has been demonstrated that trabecular bone microstructure analysis improves the prediction of bone strength beyond dual-energy X-ray absorptiometry-based bone mineral density. The purpose of this study was to obtain Magnetic Resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarkers in subjects with ISM (n=18) and compare them with those of normal controls (n=18). Trabecular bone microstructure parameters were not significantly (P>.05) different between subjects with ISM and controls. These findings revealed important pathophysiological information about ISM-associated osteoporosis and may limit the use of trabecular bone microstructure analysis in this clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Creep of trabecular bone from the human proximal tibia

Energy Technology Data Exchange (ETDEWEB)

Novitskaya, Ekaterina, E-mail: eevdokim@ucsd.edu [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Zin, Carolyn [Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218 (United States); Chang, Neil; Cory, Esther; Chen, Peter [Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); D’Lima, Darryl [Shiley Center for Orthopaedic Research and Education, Scripps Health, La Jolla, CA 92037 (United States); Sah, Robert L. [Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); McKittrick, Joanna [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States)

2014-07-01

Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for 2 h and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37 °C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. - Highlights: • Compressive creep tests of human trabecular bone across the tibia were performed. • The creep rate was found to be inversely proportional to the density of the samples. • μ-computed tomography before and after testing identified regions of deformation. • Bending of the trabeculae was found to be the main deformation mode.

Preliminary study of slow and fast ultrasonic waves using MR images of trabecular bone phantom

Energy Technology Data Exchange (ETDEWEB)

Solis-Najera, S. E., E-mail: solisnajera@ciencias.unam.mx, E-mail: angel.perez@ciencias.unam.mx, E-mail: lucia.medina@ciencias.unam.mx; Neria-Pérez, J. A., E-mail: solisnajera@ciencias.unam.mx, E-mail: angel.perez@ciencias.unam.mx, E-mail: lucia.medina@ciencias.unam.mx; Medina, L., E-mail: solisnajera@ciencias.unam.mx, E-mail: angel.perez@ciencias.unam.mx, E-mail: lucia.medina@ciencias.unam.mx [Facultad de Ciencias, Universidad Nacional Autónoma de México, México, DF 04510 (Mexico); Garipov, R., E-mail: ruslan.garipov@mrsolutions.co.uk [MR Solutions Ltd, Surrey (United Kingdom); Rodríguez, A. O., E-mail: arog@xanum.uam.mx [Departamento Ingeniería Eléctrica, Universidad Autónoma Metropolitana Iztapalapa, México, DF 09340 (Mexico)

2014-11-07

Cancellous bone is a complex tissue that performs physiological and biomechanical functions in all vertebrates. It is made up of trabeculae that, from a simplified structural viewpoint, can be considered as plates and beams in a hyperstatic structure that change with time leading to osteoporosis. Several methods has been developed to study the trabecular bone microstructure among them is the Biot’s model which predicts the existence of two longitudinal waves in porous media; the slow and the fast waves, that can be related to porosity of the media. This paper is focused on the experimental detection of the two Biot’s waves of a trabecular bone phantom, consisting of a trabecular network of inorganic hydroxyapatite. Experimental measurements of both waves were performed using through transmission ultrasound. Results had shown clearly that the propagation of two waves propagation is transversal to the trabecular alignment. Otherwise the waves are overlapped and a single wave seems to be propagated. To validate these results, magnetic resonance images were acquired to assess the trabecular direction, and to assure that the pulses correspond to the slow and fast waves. This approach offers a methodology for non-invasive studies of trabecular bones.

Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

Science.gov (United States)

Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

2016-01-01

We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Measurement of Trabecular Bone Parameters in Porcine Vertebral Bodies Using Multidetector CT: Evaluation of Reproducibility of 3-Dimensional CT Histomorphometry

Energy Technology Data Exchange (ETDEWEB)

Hong, Sung Hwan; Goo, Jin Mo [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon Kyung Chul [Dept. of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); An, Sang Bu [Dept. of radiology, National Cancer Center, Goyang (Korea, Republic of); Kim, Kwang Gi [Dept. of Biomedical Engineering, Division of Basic and Applied Sciences, National Cancer Center, Goyang (Korea, Republic of)

2011-05-15

To evaluate the reproducibility of 3-dimensional histomorphometry for the microarchitecture analysis of trabecular bone parameters using multidetector computed tomography (MDCT). Thirty-six specimens from porcine vertebral bodies were imaged five times with a 64- detector row MDCT system using the same scan protocols. Locations of the specimens were nearly identical through the scans. Three-dimensional structural parameters of trabecular bone were derived from the five data sets using image analyzing software. The features measured by the analysis programs were trabecular bone volume, trabecular bone volume/tissue volume, trabecular thickness, trabecular separation, trabecular number, trabecular bone pattern factor, structural model index. The structural trabecular parameters showed excellent reproducibility through repeated scanning. Intraclass correlation coefficients of all seven structural parameters were in the range of 0.998 to 1.000. Coefficients of variation of the six structural parameters, excluding structural model index, were not over 1.6%. The measurement of the trabecular structural parameters using multidetector CT and three-dimensional histomophometry analysis program was validated and showed excellent reproducibility. This method could be used as a noninvasive and easily available test in a clinical setting.

Distributional variations in trabecular architecture of the mandibular bone: an in vivo micro-CT analysis in rats.

Directory of Open Access Journals (Sweden)

Zhongshuang Liu

Full Text Available To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX and a sham-ovariectomy group (sham. Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012, but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005. A thickness and separation map showed that trabeculae of less than 100 μm increased by 46%, whereas trabeculae of more than 200 μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200 μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028 and bone volume fraction (p = 0.001 were also significantly decreased in the OVX group compared to the sham group.Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.

Trabecular microstructure and surface changes in the greater tuberosity in rotator cuff tears

International Nuclear Information System (INIS)

Jiang, Yebin; Zhao, Jenny; Ouyang, Xiaolong; Genant, Harry K.; Holsbeeck, Marnix T. van; Flynn, Michael J.

2002-01-01

Abstract Objective. When planning surgery in patients with rotator cuff tear, strength of bone at the tendon insertion and trabecular bone structure in the greater tuberosity are usually taken into consideration. We investigated radiographic changes in bone structure of the greater tuberosity in rotator cuff tears.Design. Twenty-two human cadaveric shoulders from subjects ranging from 55 to 75 years of age were obtained. The integrity of the rotator cuff was examined by sonography to determine if it is intact without any tear, or torn partially or completely. The humeral head was sectioned in 3 mm thick coronal slab sections and microradiographed. After digitization of the microradiographs and imaging processing with in-house semi-automated image processing software tools developed using software interfaces on a Sun workstation, the trabecular histomorphometrical structural parameters and connectivity in the greater tuberosity were quantified. The degenerative changes on the surface of the greater tuberosity were interpreted blindly by 2 independent readers.Results. Among the 22 shoulder specimens, the rotator cuff was found intact in 10 shoulders, partially in 7 and fully torn in 5. Statistically significant loss in apparent trabecular bone volume fraction, number of trabecular nodes, and number of trabecular branches, and a statistically significant increase in apparent trabecular separation and number of trabecular free ends were found in the greater tuberosity of the shoulders with tears. The loss was greater in association with full tear than in partial tear. Thickening of the cortical margin of the enthesis, irregularity of its surface, and calcification beyond the tidemark were observed in 2 (20%) shoulders with intact rotator cuff, in 6 (86%) shoulders with partial tear, and in 5 (100%) shoulders with full tear.Conclusions. Rotator cuff tears are associated with degenerative changes on the bone surface and with disuse osteopenia of the greater tuberosity

Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression

Energy Technology Data Exchange (ETDEWEB)

Lekadir, Karim, E-mail: karim.lekadir@upf.edu; Hoogendoorn, Corné [Center for Computational Imaging and Simulation Technologies in Biomedicine, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Armitage, Paul [The Academic Unit of Radiology, The University of Sheffield, Sheffield S10 2JF (United Kingdom); Whitby, Elspeth [The Academic Unit of Reproductive and Developmental Medicine, The University of Sheffield, Sheffield S10 2SF (United Kingdom); King, David [The Academic Unit of Child Health, The University of Sheffield, Sheffield S10 2TH (United Kingdom); Dimitri, Paul [The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield S10 2RX (United Kingdom); Frangi, Alejandro F. [Center for Computational Imaging and Simulation Technologies in Biomedicine, The University of Sheffield, Sheffield S1 3JD (United Kingdom)

2016-06-15

Purpose: This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. Methods: A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. Results: Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. Conclusions: The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth.

Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in trabecular meshwork cells.

Directory of Open Access Journals (Sweden)

Kate E Keller

Full Text Available Hyaluronan (HA is a major component of the extracellular matrix (ECM and is synthesized by three HA synthases (HAS. Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU, or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process.

Rationale for the evaluation of trabecular bone turnover

International Nuclear Information System (INIS)

Kimmel, D.B.; Jee, W.S.S.

1976-01-01

A procedure for the morphometric evaluation of trabecular bone is identified. Its scrupulous use allows total identification of bone formation and resorption rates, items necessary for the direct histologic analysis of bone turnover

Quasi-static and ratcheting properties of trabecular bone under uniaxial and cyclic compression.

Science.gov (United States)

Gao, Li-Lan; Wei, Chao-Lei; Zhang, Chun-Qiu; Gao, Hong; Yang, Nan; Dong, Li-Min

2017-08-01

The quasi-static and ratcheting properties of trabecular bone were investigated by experiments and theoretical predictions. The creep tests with different stress levels were completed and it is found that both the creep strain and creep compliance increase rapidly at first and then increase slowly as the creep time goes by. With increase of compressive stress the creep strain increases and the creep compliance decreases. The uniaxial compressive tests show that the applied stress rate makes remarkable influence on the compressive behaviors of trabecular bone. The Young's modulus of trabecular bone increases with increase of stress rate. The stress-strain hysteresis loops of trabecular bone under cyclic load change from sparse to dense with increase of number of cycles, which agrees with the change trend of ratcheting strain. The ratcheting strain rate rapidly decreases at first, and then exhibits a relatively stable and small value after 50cycles. Both the ratcheting strain and ratcheting strain rate increase with increase of stress amplitude or with decrease of stress rate. The creep model and the nonlinear viscoelastic constitutive model of trabecular bone were proposed and used to predict its creep property and rate-dependent compressive property. The results show that there are good agreements between the experimental data and predictions. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

Directory of Open Access Journals (Sweden)

Vanessa R. Yingling

2016-01-01

Full Text Available Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV at maturity.Methods. Female rats (25 days old were assigned to a control (C group (n = 45 that received saline injections (.2 cc or an experimental group (GnRH-a (n = 45 that received gonadotropin releasing hormone antagonist injections (.24 mg per dose for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a. The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R (n = 15 and (G-R (n = 15. The remaining animals had an ovariectomy surgery (OVX at 185 days of age and were sacrificed 40 days later (C-OVX (n = 15 and (G-OVX (n = 15. After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX and insulin-like growth factor 1 (IGF-1 were measured. Two-way ANOVA (2 groups (GnRH-a and Control X 3 time points (Injection Protocol, Recovery, post-OVX was computed.Results. GnRH-a injections suppressed uterine weights (72% and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19% following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice.

Science.gov (United States)

Han, Na-Ra; Kim, Hee-Yun; Yang, Woong Mo; Jeong, Hyun-Ja; Kim, Hyung-Min

2015-09-01

Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-β messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-β mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Finite element analysis of trabecular bone structures : a comparison of image-based meshing techniques

NARCIS (Netherlands)

Ulrich, D.; Rietbergen, van B.; Weinans, H.; Rüegsegger, P.

1998-01-01

In this study, we investigate if finite element (FE) analyses of human trabecular bone architecture based on 168 microm images can provide relevant information about the bone mechanical characteristics. Three human trabecular bone samples, one taken from the femoral head, one from the iliac crest,

Creep of trabecular bone from the human proximal tibia.

Science.gov (United States)

Novitskaya, Ekaterina; Zin, Carolyn; Chang, Neil; Cory, Esther; Chen, Peter; D'Lima, Darryl; Sah, Robert L; McKittrick, Joanna

2014-07-01

Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for 2h and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37 °C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.

Science.gov (United States)

Mori, Shuuichi; Motohashi, Norio; Takashima, Rumi; Kishi, Masahiko; Nishimune, Hiroshi; Shigemoto, Kazuhiro

2017-11-01

Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathogenicity of anti-LRP4 Abs in MG patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

Science.gov (United States)

Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites.

Science.gov (United States)

Räth, Christoph; Baum, Thomas; Monetti, Roberto; Sidorenko, Irina; Wolf, Petra; Eckstein, Felix; Matsuura, Maiko; Lochmüller, Eva-Maria; Zysset, Philippe K; Rummeny, Ernst J; Link, Thomas M; Bauer, Jan S

2013-12-01

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. μCT images were obtained with an isotropic spatial resolution of 26μm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices ( and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient β was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients β were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), -0.28 to -0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (), 0.07 to 0.11 (), -0.44 to -0.30 (σ(α)), and -0.39 to -0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of β overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60-69, 70-79, and >79years. In conclusion, the bone volume fraction-microstructure scaling relations showed a rather universal character. © 2013.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

Science.gov (United States)

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X; McMahon, Donald J; Shane, Elizabeth; Nickolas, Thomas L

2017-04-03

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

Science.gov (United States)

Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

2017-01-01

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

Directory of Open Access Journals (Sweden)

Zihui Li

Full Text Available Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (remodeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (remodeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

Prediction of mechanical properties of trabecular bone using quantitative MRI

International Nuclear Information System (INIS)

Lammentausta, E; Hakulinen, M A; Jurvelin, J S; Nieminen, M T

2006-01-01

Techniques for quantitative magnetic resonance imaging (MRI) have been developed for non-invasive estimation of the mineral density and structure of trabecular bone. The R* 2 relaxation rate (i.e. 1/T* 2 ) is sensitive to bone mineral density (BMD) via susceptibility differences between trabeculae and bone marrow, and by binarizing MRI images, structural variables, such as apparent bone volume fraction, can be assessed. In the present study, trabecular bone samples of human patellae were investigated in vitro at 1.5 T to determine the ability of MRI-derived variables (R* 2 and bone volume fraction) to predict the mechanical properties (Young's modulus, yield stress and ultimate strength). Further, the MRI variables were correlated with reference measurements of volumetric BMD and bone area fraction as determined with a clinical pQCT system. The MRI variables correlated significantly (p 2 and MRI-derived bone volume fraction further improved the prediction of yield stress and ultimate strength. Although pQCT showed a trend towards better prediction of the mechanical properties, current results demonstrate the feasibility of combined MR imaging of marrow susceptibility and bone volume fraction in predicting the mechanical strength of trabecular bone and bone mineral density

Structure model index does not measure rods and plates in trabecular bone

Directory of Open Access Journals (Sweden)

Phil L Salmon

2015-10-01

Full Text Available Structure model index (SMI is widely used to measure rods and plates in trabecular bone. It exploits the change in surface curvature that occurs as a structure varies from spherical (SMI = 4, to cylindrical (SMI = 3 to planar (SMI = 0. The most important assumption underlying SMI is that the entire bone surface is convex and that the curvature differential is positive at all points on the surface. The intricate connections within the trabecular continuum suggest that a high proportion of the surface could be concave, violating the assumption of convexity and producing regions of negative differential. We implemented SMI in the BoneJ plugin and included the ability to measure the amounts of surface that increased or decreased in area after surface mesh dilation, and the ability to visualize concave and convex regions. We measured SMI and its positive (SMI+ and negative (SMI- components, bone volume fraction (BV/TV, the fraction of the surface that is concave (CF, and mean ellipsoid factor (EF in trabecular bone using 38 X-ray microtomography (XMT images from a rat ovariectomy model of sex steroid rescue of bone loss, and 169 XMT images from a broad selection of 87 species' femora (mammals, birds, and a crocodile. We simulated bone resorption by eroding an image of elephant trabeculae and recording SMI and BV/TV at each erosion step. Up to 70%, and rarely less than 20%, of the trabecular surface is concave (CF 0.155 – 0.700. SMI is unavoidably influenced by aberrations from SMI-, which is strongly correlated with BV/TV and CF. The plate-to-rod transition in bone loss is an erroneous observation resulting from SMI's close and artefactual relationship with BV/TV. SMI cannot discern between the distinctive trabecular geometries typical of mammalian and avian bone, whereas EF clearly detects birds' more plate-like trabeculae. EF is free from confounding relationships with BV/TV and CF. SMI results reported in the literature should be treated with

Trabecular bone structure and strength - remodelling and repair

DEFF Research Database (Denmark)

Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig

2000-01-01

The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power rel......; and the hydraulic effect of the bone marrow. In order to answer these questions, more in vitro and in vivo studies on human bone in relation to aging, to immobilisation, to exercise and in relation to different treatment regimens are needed.......The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power...

Intraoperative optical coherence tomography and ab interno trabecular meshwork surgery with the Trabectome

Directory of Open Access Journals (Sweden)

Junker B

2017-09-01

Full Text Available Bernd Junker,1 Jens F Jordan,2 Carsten Framme,1 Amelie Pielen1 1University Eye Hospital, Medical School Hannover, Hannover, 2Eye Center, Medical Center, University of Freiburg, Freiburg, Germany Importance: This study is the first description of the use of the intraoperative optical coherence tomography (iOCT for trabecular meshwork surgery with the Trabectome in a regular clinical setting.Background: The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork.Design: This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover.Participants: A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study.Methods: All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients or without lens (view from above, five patients.Main outcome measures: The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork.Results: Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients.Conclusion: The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT. Keywords: glaucoma, imaging

Influence of Trabecular Bone on Peri-Implant Stress and Strain Based on Micro-CT Finite Element Modeling of Beagle Dog.

Science.gov (United States)

Liao, Sheng-Hui; Zhu, Xing-Hao; Xie, Jing; Sohodeb, Vikesh Kumar; Ding, Xi

2016-01-01

The objective of this investigation is to analyze the influence of trabecular microstructure modeling on the biomechanical distribution of the implant-bone interface. Two three-dimensional finite element mandible models, one with trabecular microstructure (a refined model) and one with macrostructure (a simplified model), were built. The values of equivalent stress at the implant-bone interface in the refined model increased compared with those of the simplified model and strain on the contrary. The distributions of stress and strain were more uniform in the refined model of trabecular microstructure, in which stress and strain were mainly concentrated in trabecular bone. It was concluded that simulation of trabecular bone microstructure had a significant effect on the distribution of stress and strain at the implant-bone interface. These results suggest that trabecular structures could disperse stress and strain and serve as load buffers.

Assessment of jawbone trabecular bone structure amongst osteoporotic women by cone-beam computed tomography: the OSTEOSYR project.

Science.gov (United States)

Barngkgei, Imad; Al Haffar, Iyad; Shaarani, Eyad; Khattab, Razan; Mashlah, Ammar

2016-11-01

To assess the trabecular bone structure of jawbones and the dens (the odontoid process of the second cervical vertebra) amongst osteoporotic and nonosteoporotic women using cone-beam computed tomography (CBCT). Analysis of the dens trabecular bone structure aimed to test the validity of CBCT in such analysis. Thirty-eight women who went under dual-energy X-ray absorptiometry (DXA) examination were scanned by CBCT. Cuboids from different areas of jawbones and the dens were extracted from each scan. Trabecular thickness (Tb.Th), trabecular separation (Tb.S), bone volume fraction (BV/TV), specific bone surface (BS/TV) and connectivity density were calculated. Student's t-test, Pearson correlation, and logistic regression analysis were used to explore differences in these measures between groups. Jawbone-derived measures showed insignificant differences (P > 0.05) between osteoporotic and non-osteoporotic groups, and weak correlations with femoral neck and lumbar vertebrae T-scores (r ≤ 0.4). Dens-derived measures, however, resulted in the opposite (r = 0.34-0.38 [P value = 0.02-0.036] and r = 0.48-0.61 [P value ≤ 0.003]) and the highest accuracy of osteoporosis prediction: 84.2% and 78.9% respectively. Trabecular bone structure of the mandible and maxilla is not affected in osteoporosis as assessed by CBCT. Dens trabecular bone analysis revealed the opposite, so some trabecular bone measures may be assessed by CBCT, which may aid in predicting osteoporosis. © 2015 Wiley Publishing Asia Pty Ltd.

Inhibitory effects on bone resorption in postmenopausal osteoporosis model mice by delivery of serum calcium decreasing factor (caldecrin) gene

International Nuclear Information System (INIS)

Oi, Michi; Kido, Seisui; Hasegawa, Hiroya; Fujimoto, Kengo; Tomomura, Mineko; Kanegae, Haruhide; Suda, Naoto; Tomomura, Akito

2011-01-01

Osteoporosis is a common condition in which decrease in the bone volume and strength occurs due to increased bone resorption. Caldecrin is a serine protease, with a molecular weight of 28kDa, and it is the causative factor of hypocalcemia frequently seen in acute pancreatitis. Recent reports have shown that caldecrin also acts to inhibit both differentiation of the osteoclasts and function of the mature osteoclasts. In this study, the osteoporosis model mice were used and bilateral ovariectomy was conducted in these mice. Effect of bone absorption was estimated after introducing genetically the pCaldecrin-IRES-hrGFP expressing vector into the femoral muscle by use of the hemagglutinating virus of Japan (HVJ)-liposomes. After the bilateral ovariectomy, serum calcium levels were raised and the bone mass of the femur was decreased. However, in the genetically introduced groups of the model mice, serum calcium levels were significantly lowered. Concomitantly, significant increase in bone density, trabecular width and number of trabecular was observed. Moreover, based on the histological findings, inhibition of bone resorption in the caldecrin-introduced osteoporosis model mice was confirmed. The present study indicates that caldecrin can be expected to become a novel cure for osteoporosis. (author)

Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

Science.gov (United States)

The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

Variability of morphometric parameters of human trabecular tissue from coxo-arthritis and osteoporotic samples

Directory of Open Access Journals (Sweden)

Franco Marinozzi

2012-01-01

Full Text Available Morphometric and architectural bone parameters change in diseases such as osteoarthritis and osteoporosis. The mechanical strength of bone is primarily influenced by bone quantity and quality. Bone quality is defined by parameters such as trabecular thickness, trabecular separation, trabecular density and degree of anisotropy that describe the micro-architectural structure of bone. Recently, many studies have validated microtomography as a valuable investigative technique to assess bone morphometry, thanks to micro-CT non-destructive, non-invasive and reliability features, in comparison to traditional techniques such as histology. The aim of this study is the analysis by micro-computed tomography of six specimens, extracted from patients affected by osteoarthritis and osteoporosis, in order to observe the tridimensional structure and calculate several morphometric parameters.

Copas de metal trabecular y aloinjertos óseos impactados en defectos acetabulares graves. Resultados a los 2-4 años. [Impacted bone allografts and trabecular metal cups in severe acetabular bone defects: 2 to 4-year results.

Directory of Open Access Journals (Sweden)

Martín Buttaro

2014-06-01

Full Text Available In­tro­duc­ción: El objetivo principal es presentar la supervivencia del componente acetabular en pacientes con defectos graves reconstruidos con copas de metal trabecular combinadas con aloinjertos óseos impactados. Como objetivo secundario, se compararon estos resultados con los previamente obtenidos por los autores en defectos de similar gravedad utilizando anillos de reconstrucción y aloinjertos óseos. Materiales­ y­ Métodos:­ Se realizaron 20 cirugías de revisión en 19 pacientes (edad promedio 65 años, controlados, de forma prospectiva, con defectos acetabulares graves tipos 3A o 3B de Paprosky, por falla mecánica o infecciosa. El puntaje funcional promedio preoperatorio fue de 6,2 puntos, según la escala de Merle D ́Aubigne. Siempre se utilizaron copas de metal trabecular y aloinjertos óseos impactados. Resultados:­ A los 30 meses de seguimiento promedio (rango 24-48 meses, la supervivencia del componente acetabular fue del 95% (IC = 75%-98%. Un paciente presentó un aflojamiento acetabular por infección profunda a las 16 semanas de la revisión y fue tratado con una artroplastia de resección. El puntaje funcional promedio, excluido el caso con aflojamiento posoperatorio, fue de 16,2 puntos. Se observó la incorporación de los aloinjertos óseos en todos los pacientes, salvo el caso con infección profunda. La comparación con nuestras series históricas reconstruidas con anillos de Kerboull o con anillos GAP arrojó resultados altamente favorables a favor de las copas de metal trabecular.  Conclusiones: Las copas de metal trabecular asociadas a aloinjertos óseos impactados ofrecen una alternativa válida en cirugía de revisión acetabular con defectos graves del capital óseo. Este método se asocia a resultados más favorables que los obtenidos antes con anillos de reconstrucción.

Total water, phosphorus relaxation and inter-atomic organic to inorganic interface are new determinants of trabecular bone integrity.

Directory of Open Access Journals (Sweden)

Ratan Kumar Rai

Full Text Available Bone is the living composite biomaterial having unique structural property. Presently, there is a considerable gap in our understanding of bone structure and composition in the native state, particularly with respect to the trabecular bone, which is metabolically more active than cortical bones, and is readily lost in post-menopausal osteoporosis. We used solid-state nuclear magnetic resonance (NMR to compare trabecular bone structure and composition in the native state between normal, bone loss and bone restoration conditions in rat. Trabecular osteopenia was induced by lactation as well as prolonged estrogen deficiency (bilateral ovariectomy, Ovx. Ovx rats with established osteopenia were administered with PTH (parathyroid hormone, trabecular restoration group, and restoration was allowed to become comparable to sham Ovx (control group using bone mineral density (BMD and µCT determinants. We used a technique combining (1H NMR spectroscopy with (31P and (13C to measure various NMR parameters described below. Our results revealed that trabecular bones had diminished total water content, inorganic phosphorus NMR relaxation time (T1 and space between the collagen and inorganic phosphorus in the osteopenic groups compared to control, and these changes were significantly reversed in the bone restoration group. Remarkably, bound water was decreased in both osteopenic and bone restoration groups compared to control. Total water and T1 correlated strongly with trabecular bone density, volume, thickness, connectivity, spacing and resistance to compression. Bound water did not correlate with any of the microarchitectural and compression parameters. We conclude that total water, T1 and atomic space between the crystal and organic surface are altered in the trabecular bones of osteopenic rats, and PTH reverses these parameters. Furthermore, from these data, it appears that total water and T1 could serve as trabecular surrogates of micro-architecture and

Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

International Nuclear Information System (INIS)

Arioka, Masaki; Takahashi-Yanaga, Fumi; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki

2013-01-01

Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β +/− mice. •The cortical and trabecular bone volumes were increased in GSK-3β +/− mice. •Regeneration of a partial bone defect was accelerated in GSK-3β +/− mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β +/− ). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β +/− mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β +/− mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β +/− mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β +/− mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway

Measurement of the speed of sound in trabecular bone by using a time reversal acoustics focusing system

Energy Technology Data Exchange (ETDEWEB)

Lee, Kang Il [Kangwon National University, Chuncheon (Korea, Republic of); Choi, Bok-Kyoung [Maritime Security Research Center, KIOST, Ansan (Korea, Republic of)

2014-10-15

A new method for measuring the speed of sound (SOS) in trabecular bone by using a time reversal acoustics (TRA) focusing system was proposed and validated with measurements obtained by using the conventional pulse-transmission technique. The SOS measured in 14 bovine femoral trabecular bone samples by using the two methods was highly correlated each other, although the SOS measured by using the TRA focusing system was slightly lower by an average of 2.2 m/s. The SOS measured by using the two methods showed high correlation coefficients of r = 0.92 with the apparent bone density, consistent with the behavior in human trabecular bone in vitro. These results prove the efficacy of the new method based on the principle of TRA to measure the SOS in trabecular bone.

A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

Science.gov (United States)

Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K

2015-04-01

Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

Directory of Open Access Journals (Sweden)

Quan Yuan

Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats.

Science.gov (United States)

Levkovitch-Verbin, Hana; Quigley, Harry A; Martin, Keith R G; Valenta, Danielle; Baumrind, Lisa A; Pease, Mary Ellen

2002-02-01

To develop and characterize a model of pressure-induced optic neuropathy in rats. Experimental glaucoma was induced unilaterally in 174 Wistar rats, using a diode laser with wavelength of 532 nm aimed at the trabecular meshwork and episcleral veins (combination treatment group) or only at the trabecular meshwork (trabecular group) through the external limbus. Intraocular pressure (IOP) was measured by a tonometer in rats under ketamine-xylazine anesthesia. Possible retinal vascular compromise was evaluated by repeated fundus examinations and by histology. The degree of retinal ganglion cell (RGC) loss was assessed by a masked, semiautomated counting of optic nerve axons. Effects of laser treatment on anterior ocular structures and retina were judged by light microscopy. After the laser treatment, IOP was increased in all eyes to higher than the normal mean IOP of 19.4 +/- 2.1 mm Hg (270 eyes). Peak IOP was 49.0 +/- 6.1 mm Hg (n = 108) in the combination group that was treated by a laser setting of 0.7 seconds and 0.4 W and 34.0 +/- 5.7 mm Hg (n = 46) in the trabecular group. Mean IOP after 6 weeks was 25.5 +/- 2.9 mm Hg in glaucomatous eyes in the combination group compared with 22.0 +/- 1.8 mm Hg in the trabecular group. IOP in the glaucomatous eyes was typically higher than in the control eyes for at least 3 weeks. In the combination group, RGC loss was 16.1% +/- 14.4% at 1 week (n = 8, P = 0.01), 59.7% +/- 25.7% at 6 weeks (n = 88, P < 0.001), and 70.9% +/- 23.6% at 9 weeks (n = 12, P < 0.001). The trabecular group had mean axonal loss of 19.1% +/- 14.0% at 3 weeks (n = 9, P = 0.004) and 24.3% +/- 20.2% at 6 weeks (n = 25, P < 0.001), increasing to 48.4% +/- 32.8% at 9 weeks (n = 12, P < 0.001). Laser treatment led to closure of intertrabecular spaces and the major outflow channel. The retina and choroid were normal by ophthalmoscopy at all times after treatment. Light microscopic examination showed only loss of RGCs and their nerve fibers. Increased IOP caused

In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).

Science.gov (United States)

Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

2012-12-01

Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.

NUMERICAL AND MECHANICAL ANALYSES OF A 3D-PRINTED TITANIUM TRABECULAR DENTAL IMPLANT

Directory of Open Access Journals (Sweden)

Luboš Řehounek

2017-06-01

Full Text Available The main focus of this paper is to investigate and describe a novel biomaterial structure. The trabecular structure has only recently been recognized as a viable alternative for prostheses and implants and seems to have very promising biocompatibility and mechanical properties. The 3D printing technique was used to create test specimens. These specimens were then tested by nanoindentation and tensile and compression tests. A numerical model was created and curve-fitted to represent the mechanical behavior of the trabecular structure. A significant reduction in the values of Young’s modulus E was observed. The values of E for conventional implant materials are approximately 110–120GPa and the trabecular structure reached a value just below 1GPa. The next effort will be to apply the model onto a real implant. It is the “four leaf clover” implant variant by authors F. Denk Jr., A. Jíra and F. Denk Sr.

A high-fat diet induces bone loss in mice lacking the Alox5 gene.

Science.gov (United States)

Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

2012-01-01

5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

Fractal analysis of mandibular trabecular bone: optimal tile sizes for the tile counting method.

Science.gov (United States)

Huh, Kyung-Hoe; Baik, Jee-Seon; Yi, Won-Jin; Heo, Min-Suk; Lee, Sam-Sun; Choi, Soon-Chul; Lee, Sun-Bok; Lee, Seung-Pyo

2011-06-01

This study was performed to determine the optimal tile size for the fractal dimension of the mandibular trabecular bone using a tile counting method. Digital intraoral radiographic images were obtained at the mandibular angle, molar, premolar, and incisor regions of 29 human dry mandibles. After preprocessing, the parameters representing morphometric characteristics of the trabecular bone were calculated. The fractal dimensions of the processed images were analyzed in various tile sizes by the tile counting method. The optimal range of tile size was 0.132 mm to 0.396 mm for the fractal dimension using the tile counting method. The sizes were closely related to the morphometric parameters. The fractal dimension of mandibular trabecular bone, as calculated with the tile counting method, can be best characterized with a range of tile sizes from 0.132 to 0.396 mm.

Long range node-strut analysis of trabecular bone microarchitecture

DEFF Research Database (Denmark)

Schmah, Tanya; Marwan, Norbert; Thomsen, Jesper Skovhus

2011-01-01

PURPOSE: We present a new morphometric measure of trabecular bone microarchitecture, called mean node strength (NdStr), which is part of a newly developed approach called long range node-strut analysis. Our general aim is to describe and quantify the apparent "latticelike" microarchitecture of th...

Dosimetric validation of synthetic trabecular bone generated by parametric Monte Carlo Method; Validação dosimétrica de trabéculas ósseas sintéticas geradas por método Monte Carlo paramétrico

Energy Technology Data Exchange (ETDEWEB)

Oliveira, F.G.; Andrade, A.F.G. de; Vieira, J.W., E-mail: baby.oliveira@hotmail.com.br, E-mail: arthurfelandrade@gmail.com, E-mail: jose.wilson59@uol.com.br [Instituto Federal de Pernambuco (IFPE), Recife, PE (Brazil); Oliveira, A.C.H. de, E-mail: oliveira_ach@yahoo.com [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil); Lima, F.R.A., E-mail: falima@cnen.gov.br [Centro Regional de Ciências Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife-PE (Brazil)

2017-07-01

One of the greatest challenges of numerical dosimetry is to estimate the dose of ionizing radiation absorbed by the soft tissues that are located in bone trabecular. Due to the difficulty in obtaining micro-CT images of real bone samples (OR), the need for the generation of synthetic bone trabecular appeared. In this work, virtual synthetic trabecular samples (BU), generated by Monte Carlo methods parameterized by the Burr XII probability density function (FDP), and their OR equivalents were submitted to dosimetric evaluations in the adult male Computational Exposure Model (MCE) in orthostatic position (MSTA) coupled to the EGSnrc software with idealized photon-emitting sources and targeting the two most radiosensitive bone tissues: red bone marrow and the foramen-bone surface of trabecular bones, sternum, spine, femur, pelvis and skull regions. When comparing the dosimetric results of the two sample sets, it was found that the overall relative error presented was 4.34%. It is concluded that the synthetic trabecular generated by FDPs with the same characteristics as the Burr XII FDP can successfully replace the OR bones in similar bone dosimetry tests.

Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice.

Science.gov (United States)

Yan, Lin; Graef, George L; Nielsen, Forrest H; Johnson, LuAnn K; Cao, Jay

2015-06-01

Physical activity and soy protein isolate (SPI) augmentation have been reported to be beneficial for bone health. We hypothesized that combining voluntary running and SPI intake would alleviate detrimental changes in bone induced by a high-fat diet. A 2 × 2 × 2 experiment was designed with diets containing 16% or 45% of energy as corn oil and 20% SPI or casein fed to sedentary or running male C57BL/6 mice for 14 weeks. Distal femurs were assessed for microstructural changes. The high-fat diet significantly decreased trabecular number (Tb.N) and bone mineral density (BMD) and increased trabecular separation (Tb.Sp). Soy protein instead of casein, regardless of fat content, in the diet significantly increased bone volume fraction, Tb.N, connectivity density, and BMD and decreased Tb.Sp. Voluntary running, regardless of fat content, significantly decreased bone volume fraction, Tb.N, connectivity density, and BMD and increased Tb.Sp. The high-fat diet significantly decreased osteocalcin and increased tartrate-resistant acid phosphatase 5b (TRAP 5b) concentrations in plasma. Plasma concentrations of osteocalcin were increased by both SPI and running. Running alleviated the increase in TRAP 5b induced by the high-fat diet. These findings demonstrate that a high-fat diet is deleterious, and SPI is beneficial to trabecular bone properties. The deleterious effect of voluntary running on trabecular structural characteristics indicates that there may be a maximal threshold of running beyond which beneficial effects cease and detrimental effects occur. Increases in plasma osteocalcin and decreases in plasma TRAP 5b in running mice suggest that a compensatory response occurs to counteract the detrimental effects of excessive running. Published by Elsevier Inc.

Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

Energy Technology Data Exchange (ETDEWEB)

Arioka, Masaki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Takahashi-Yanaga, Fumi, E-mail: yanaga@clipharm.med.kyushu-u.ac.jp [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Sasaki, Masanori [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Yoshihara, Tatsuya; Morimoto, Sachio [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Takashima, Akihiko [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan); Mori, Yoshihide [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Sasaguri, Toshiyuki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)

2013-11-01

Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

Age-related changes in cortical and trabecular bone mineral status: A quantitative CT study in lumbar vertebrae

International Nuclear Information System (INIS)

Tanno, M.; Horiuchi, T.; Nakajima, I.; Maeda, S.; Igarashi, M.; Yamada, H.

2000-01-01

To investigate the age and sex dependence of the bone mineral status of human lumbar vertebrae with special regard to differences between cortical and trabecular bone. The study group comprised 125 normal Japanese healthy volunteers (54 males and 71 females), and was subdivided into adult male and female groups (subjects younger than 40 years), intermediate male and female groups (ages ranging between 41 and 64 years) and old male and female groups (subjects older than 65 years). The cortical bone mineral status was estimated using a single-energy quantitative CT (SE-QCT) technique, whereas trabecular bone mineral density (BMD) was estimated using a dual-energy (DE-QCT) technique. A considerable gender difference in the age-related cortical bone status was found. There was a significant reduction of the mean values of the cortical volume and BMD in the old female group compared with those obtained in the old male group. The results suggest that in men, cortical and trabecular bone volume decrease very little with age. In women, cortical volume and BMD and trabecular BMD decrease with age while trabecular bone volume does not. The study showed that all variables had higher values in men than in women and that the difference increased with age

Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

Directory of Open Access Journals (Sweden)

Tracy A. Brennan

2014-05-01

Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn�

Diagnosis of osteoarthritis and prognosis of tibial cartilage loss by quantification of tibia trabecular bone from MRI

DEFF Research Database (Denmark)

Marques, Joselene; Genant, Harry K.; Lillholm, Martin

2013-01-01

loss were assessed by a segmentation process. Aiming to quantify and potentially capture the structure of the trabecular bone anatomy, a machine learning approach used a set of texture features for training a classifier to recognize the trabecular bone of a knee with radiographic osteoarthritis. Using...

Osteoporosis imaging: effects of bone preservation on MDCT-based trabecular bone microstructure parameters and finite element models

International Nuclear Information System (INIS)

Baum, Thomas; Grande Garcia, Eduardo; Burgkart, Rainer; Gordijenko, Olga; Liebl, Hans; Jungmann, Pia M.; Gruber, Michael; Zahel, Tina; Rummeny, Ernst J.; Waldt, Simone; Bauer, Jan S.

2015-01-01

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength due to a reduction of bone mass and deterioration of bone microstructure predisposing an individual to an increased risk of fracture. Trabecular bone microstructure analysis and finite element models (FEM) have shown to improve the prediction of bone strength beyond bone mineral density (BMD) measurements. These computational methods have been developed and validated in specimens preserved in formalin solution or by freezing. However, little is known about the effects of preservation on trabecular bone microstructure and FEM. The purpose of this observational study was to investigate the effects of preservation on trabecular bone microstructure and FEM in human vertebrae. Four thoracic vertebrae were harvested from each of three fresh human cadavers (n = 12). Multi-detector computed tomography (MDCT) images were obtained at baseline, 3 and 6 month follow-up. In the intervals between MDCT imaging, two vertebrae from each donor were formalin-fixed and frozen, respectively. BMD, trabecular bone microstructure parameters (histomorphometry and fractal dimension), and FEM-based apparent compressive modulus (ACM) were determined in the MDCT images and validated by mechanical testing to failure of the vertebrae after 6 months. Changes of BMD, trabecular bone microstructure parameters, and FEM-based ACM in formalin-fixed and frozen vertebrae over 6 months ranged between 1.0–5.6 % and 1.3–6.1 %, respectively, and were not statistically significant (p > 0.05). BMD, trabecular bone microstructure parameters, and FEM-based ACM as assessed at baseline, 3 and 6 month follow-up correlated significantly with mechanically determined failure load (r = 0.89–0.99; p < 0.05). The correlation coefficients r were not significantly different for the two preservation methods (p > 0.05). Formalin fixation and freezing up to six months showed no significant effects on trabecular bone microstructure

Relationships of the phase velocity with the microarchitectural parameters in bovine trabecular bone in vitro: Application of a stratified model

Science.gov (United States)

Lee, Kang Il

2012-08-01

The present study aims to provide insight into the relationships of the phase velocity with the microarchitectural parameters in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 22 bovine femoral trabecular bone samples by using a pair of transducers with a diameter of 25.4 mm and a center frequency of 0.5 MHz. The phase velocity exhibited positive correlation coefficients of 0.48 and 0.32 with the ratio of bone volume to total volume and the trabecular thickness, respectively, but a negative correlation coefficient of -0.62 with the trabecular separation. The best univariate predictor of the phase velocity was the trabecular separation, yielding an adjusted squared correlation coefficient of 0.36. The multivariate regression models yielded adjusted squared correlation coefficients of 0.21-0.36. The theoretical phase velocity predicted by using a stratified model for wave propagation in periodically stratified media consisting of alternating parallel solid-fluid layers showed reasonable agreements with the experimental measurements.

Strain rate dependency of bovine trabecular bone under impact loading at sideways fall velocity.

Science.gov (United States)

Enns-Bray, William S; Ferguson, Stephen J; Helgason, Benedikt

2018-05-03

There is currently a knowledge gap in scientific literature concerning the strain rate dependent properties of trabecular bone at intermediate strain rates. Meanwhile, strain rates between 10 and 200/s have been observed in previous dynamic finite element models of the proximal femur loaded at realistic sideways fall speeds. This study aimed to quantify the effect of strain rate (ε̇) on modulus of elasticity (E), ultimate stress (σ u ), failure energy (U f ), and minimum stress (σ m ) of trabecular bone in order to improve the biofidelity of material properties used in dynamic simulations of sideways fall loading on the hip. Cylindrical cores of trabecular bone (D = 8 mm, L gauge  = 16 mm, n = 34) from bovine proximal tibiae and distal femurs were scanned in µCT (10 µm), quantifying apparent density (ρ app ) and degree of anisotropy (DA), and subsequently impacted within a miniature drop tower. Force of impact was measured using a piezoelectric load cell (400 kHz), while displacement during compression was measured from high speed video (50,000 frames/s). Four groups, with similar density distributions, were loaded at different impact velocities (0.84, 1.33, 1.75, and 2.16 m/s) with constant kinetic energy (0.4 J) by adjusting the impact mass. The mean strain rates of each group were significantly different (p < 0.05) except for the two fastest impact speeds (p = 0.09). Non-linear regression models correlated strain rate, DA, and ρ app with ultimate stress (R 2  = 0.76), elastic modulus (R 2  = 0.63), failure energy (R 2  = 0.38), and minimum stress (R 2  = 0.57). These results indicate that previous estimates of σ u could be under predicting the mechanical properties at strain rates above 10/s. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of different loading patterns on the trabecular bone morphology of the proximal femur using adaptive bone remodeling.

Science.gov (United States)

Banijamali, S Mohammad Ali; Oftadeh, Ramin; Nazarian, Ara; Goebel, Ruben; Vaziri, Ashkan; Nayeb-Hashemi, Hamid

2015-01-01

In this study, the changes in the bone density of human femur model as a result of different loadings were investigated. The model initially consisted of a solid shell representing cortical bone encompassing a cubical network of interconnected rods representing trabecular bone. A computationally efficient program was developed that iteratively changed the structure of trabecular bone by keeping the local stress in the structure within a defined stress range. The stress was controlled by either enhancing existing beam elements or removing beams from the initial trabecular frame structure. Analyses were performed for two cases of homogenous isotropic and transversely isotropic beams.Trabecular bone structure was obtained for three load cases: walking, stair climbing and stumbling without falling. The results indicate that trabecular bone tissue material properties do not have a significant effect on the converged structure of trabecular bone. In addition, as the magnitude of the loads increase, the internal structure becomes denser in critical zones. Loading associated with the stumbling results in the highest density;whereas walking, considered as a routine daily activity, results in the least internal density in different regions. Furthermore, bone volume fraction at the critical regions of the converged structure is in good agreement with previously measured data obtained from combinations of dual X-ray absorptiometry (DXA) and computed tomography (CT). The results indicate that the converged bone architecture consisting of rods and plates are consistent with the natural bone morphology of the femur. The proposed model shows a promising means to understand the effects of different individual loading patterns on the bone density.

Three-dimensional trabecular bone architecture of the lumbar spine in bone metastasis from prostate cancer: comparison with degenerative sclerosis

International Nuclear Information System (INIS)

Tamada, Tsutomu; Sone, Teruki; Imai, Shigeki; Kajihara, Yasumasa; Fukunaga, Masao; Jo, Yoshimasa

2005-01-01

Prostate cancer frequently metastasizes to bone, inducing osteosclerotic lesions. The objective of this study was to clarify the three-dimensional (3D) trabecular bone microstructure in bone metastasis from prostate cancer by comparison with normal and degenerative sclerotic bone lesions, using microcomputed tomography (micro-CT). A total of 32 cancellous bone samples were excised from the lumbar spine of six autopsy patients: 15 metastatic samples (one patient), eight degenerative sclerotic samples (four patients) and the rest from normal sites (three patients). The samples were serially scanned cross-sectionally by micro-CT with a pixel size of 23.20 μm, slice thickness of 18.56 μm, and image matrix of 512 x 512. Each image data set consisted of 250 consecutive slices. The volumes of interest (96 x 96 x 120 voxels) were defined in the original image sets and 3D indices of the trabecular microstructure were determined. The trabecular thickness (Tb.Th) in degenerative sclerotic lesions was significantly higher than that in normal sites, whereas no significant difference was observed in trabecular number (Tb.N). By contrast, in metastatic lesions, the Tb.N was significantly higher with increased bone volume fraction (BV/TV) than in normal sites, and no significant difference was found in Tb.Th. The characteristics of the trabecular surface in the metastatic samples showed concave structural elements with an increase in BV/TV, indicating osteolysis of the trabecular bone. In 3D reconstructed images, increased trabecular bone with an irregular surface was observed in samples from metastatic sites, which were uniformly sclerotic on soft X-ray radiographs. These results support, through 3D morphological features, the strong bone resorption effect in bone metastasis from prostate cancer. (orig.)

[Analysis of correlation between trabecular microstructure and clinical imaging parameters in fracture region of osteoporotic hip].

Science.gov (United States)

Peng, Jing; Zhou, Yong; Min, Li; Zhang, Wenli; Luo, Yi; Zhang, Xuelei; Zou, Chang; Shi, Rui; Tu, Chongqi

2014-05-01

To analyze the correlation between the trabecular microstructure and the clinical imaging parameters in the fracture region of osteoporotic hip so as to provide a simple method to evaluate the trabecular microstructure by a non-invasive way. Between June 2012 and January 2013, 16 elderly patients with femoral neck fracture underwent hip arthroplasty were selected as the trial group; 5 young patients with pelvic fracture were selected as the control group. The hip CT examination was done, and cancellous bone volume/marrow cavity volume (CV/MV) was analyzed with Mimics 10.01 software in the control group. The CT scan and bone mineral density (BMD) measurement were performed on normal hips of the trial group, and cuboid specimens were gained from the femoral necks at the place of the tensional trabeculae to evaluate the trabecular microstructure parameters by Micro-CT, including bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular spacing (Tb.Sp), trabecular thickness (Tb.Th), connect density (Conn.D), and structure model index (SMI). The correlation between imaging parameters and microstructure parameters was analyzed. In the trial group, the BMD value was 0.491-0.698 g/cm2 (mean, 0.601 g/cm2); according to World Health Organization (WHO) standard, 10 cases were diagnosed as having osteoporosis, and 6 cases as having osteopenia. The CV/MV of the trial group (0.670 1 +/- 0.102 0) was significantly lower than that of the control group (0.885 0 +/- 0.089 1) (t = -4.567, P = 0.000). In the trial group, CV/MV had correlation with BV/TV, Tb.Th, and SMI (P 0.05). BV/TV had correlation with Tb.Th, Tb.N, Tb.Sp, and SMI (P microstructure parameters (P > 0.05). CV/MV obviously decreases in the osteoporotic hip, and there is a correlation between CV/MV and the microstructure parameters of BV/TV, Tb.Th, and SMI, to some extent, which can reflect the variety of the microstructure of the trabeculae. There is no correlation between BMD of femoral neck and

A synchrotron radiation microtomography system for the analysis of trabecular bone samples.

Science.gov (United States)

Salomé, M; Peyrin, F; Cloetens, P; Odet, C; Laval-Jeantet, A M; Baruchel, J; Spanne, P

1999-10-01

X-ray computed microtomography is particularly well suited for studying trabecular bone architecture, which requires three-dimensional (3-D) images with high spatial resolution. For this purpose, we describe a three-dimensional computed microtomography (microCT) system using synchrotron radiation, developed at ESRF. Since synchrotron radiation provides a monochromatic and high photon flux x-ray beam, it allows high resolution and a high signal-to-noise ratio imaging. The principle of the system is based on truly three-dimensional parallel tomographic acquisition. It uses a two-dimensional (2-D) CCD-based detector to record 2-D radiographs of the transmitted beam through the sample under different angles of view. The 3-D tomographic reconstruction, performed by an exact 3-D filtered backprojection algorithm, yields 3-D images with cubic voxels. The spatial resolution of the detector was experimentally measured. For the application to bone investigation, the voxel size was set to 6.65 microm, and the experimental spatial resolution was found to be 11 microm. The reconstructed linear attenuation coefficient was calibrated from hydroxyapatite phantoms. Image processing tools are being developed to extract structural parameters quantifying trabecular bone architecture from the 3-D microCT images. First results on human trabecular bone samples are presented.

Relationships of the phase velocity with the micro architectural parameters in bovine trabecular bone in vitro: application of a stratified model

Energy Technology Data Exchange (ETDEWEB)

Lee, Kang Il [Kangwon National University, Chuncheon (Korea, Republic of)

2012-08-15

The present study aims to provide insight into the relationships of the phase velocity with the micro architectural parameters in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 22 bovine femoral trabecular bone samples by using a pair of transducers with a diameter of 25.4 mm and a center frequency of 0.5 MHz. The phase velocity exhibited positive correlation coefficients of 0.48 and 0.32 with the ratio of bone volume to total volume and the trabecular thickness, respectively, but a negative correlation coefficient of -0.62 with the trabecular separation. The best univariate predictor of the phase velocity was the trabecular separation, yielding an adjusted squared correlation coefficient of 0.36. The multivariate regression models yielded adjusted squared correlation coefficients of 0.21 - 0.36. The theoretical phase velocity predicted by using a stratified model for wave propagation in periodically stratified media consisting of alternating parallel solid-fluid layers showed reasonable agreements with the experimental measurements.

Relationships of the phase velocity with the micro architectural parameters in bovine trabecular bone in vitro: application of a stratified model

International Nuclear Information System (INIS)

Lee, Kang Il

2012-01-01

The present study aims to provide insight into the relationships of the phase velocity with the micro architectural parameters in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 22 bovine femoral trabecular bone samples by using a pair of transducers with a diameter of 25.4 mm and a center frequency of 0.5 MHz. The phase velocity exhibited positive correlation coefficients of 0.48 and 0.32 with the ratio of bone volume to total volume and the trabecular thickness, respectively, but a negative correlation coefficient of -0.62 with the trabecular separation. The best univariate predictor of the phase velocity was the trabecular separation, yielding an adjusted squared correlation coefficient of 0.36. The multivariate regression models yielded adjusted squared correlation coefficients of 0.21 - 0.36. The theoretical phase velocity predicted by using a stratified model for wave propagation in periodically stratified media consisting of alternating parallel solid-fluid layers showed reasonable agreements with the experimental measurements.

Similar efficacy from specific and non-specific mineralocorticoid receptor antagonist treatment of muscular dystrophy mice.

Science.gov (United States)

Lowe, Jeovanna; Floyd, Kyle T; Rastogi, Neha; Schultz, Eric J; Chadwick, Jessica A; Swager, Sarah A; Zins, Jonathan G; Kadakia, Feni K; Smart, Suzanne; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E; Raman, Subha V; Janssen, Paul M L; Rafael-Fortney, Jill A

2016-01-01

Combined treatment with an angiotensin-converting enzyme inhibitor and a mineralocorticoid receptor (MR) antagonist improved cardiac and skeletal muscle function and pathology in a mouse model of Duchenne muscular dystrophy. MR is present in limb and respiratory skeletal muscles and functions as a steroid hormone receptor. The goals of the current study were to compare the efficacy of the specific MR antagonist eplerenone with the non-specific MR antagonist spironolactone, both in combination with the angiotensin-converting enzyme inhibitor lisinopril. Three groups of n=18 dystrophin-deficient, utrophin-haploinsufficient male mice were given chow containing: lisinopril plus spironolactone, lisinopril plus eplerenone, or no drug, from four to 20 weeks-of-age. Eighteen C57BL/10 male mice were used as wild-type controls. In vivo measurements included cardiac magnetic resonance imaging, conscious electrocardiography, and grip strength. From each mouse in the study, diaphragm, extensor digitorum longus , and cardiac papillary muscle force was measured ex vivo , followed by histological quantification of muscle damage in heart, diaphragm, quadriceps, and abdominal muscles. MR protein levels were also verified in treated muscles. Treatment with specific and non-specific MR antagonists did not result in any adverse effects to dystrophic skeletal muscles or heart. Both treatments resulted in similar functional and pathological improvements across a wide array of parameters. MR protein levels were not reduced by treatment. These data suggest that spironolactone and eplerenone show similar effects in dystrophic mice and support the clinical development of MR antagonists for treating skeletal muscles in Duchenne muscular dystrophy.

Effect of spaceflight hardware on the skeletal properties of ground control mice

Science.gov (United States)

Bateman, Ted; Lloyd, Shane; Dunlap, Alex; Ferguson, Virginia; Simske, Steven; Stodieck, Louis; Livingston, Eric

Introduction: Spaceflight experiments using mouse or rat models require habitats that are specifically designed for the microgravity environment. During spaceflight, rodents are housed in a specially designed stainless steel meshed cage with gravity-independent food and water delivery systems and constant airflow to push floating urine and feces towards a waste filter. Differences in the housing environment alone, not even considering the spaceflight environment itself, may lead to physiological changes in the animals contained within. It is important to characterize these cage differences so that results from spaceflight experiments can be more reliably compared to studies from other laboratories. Methods: For this study, we examined the effect of NASA's Animal Enclosure Module (AEM) spaceflight hardware on the skeletal properties of 8-week-old female C57BL/6J mice. This 13-day experiment, conducted on the ground, modeled the flight experiment profile of the CBTM-01 payload on STS-108, with standard vivarium-housed mice being compared to AEM-housed mice (n = 12/group). Functional differences were compared via mechanical testing, micro-hardness indentation, microcomputed tomography, and mineral/matrix composition. Cellular changes were examined by serum chemistry, histology, quantitative histomorphometry, and RT-PCR. A Student's t-test was utilized, with the level of Type I error set at 95 Results: There was no change in elastic, maximum, or fracture force mechanical properties at the femur mid-diaphysis, however, structural stiffness was -17.5 Conclusions: Housing mice in the AEM spaceflight hardware had minimal effects on femur cortical bone properties. However, trabecular bone at the proximal tibia in AEM mice experi-enced large increases in microarchitecture and mineral composition. Increases in bone density were accompanied by reductions in bone-forming osteoblasts and bone-resorbing osteoclasts, representing a general decline in bone turnover at this site

Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits: an in-vivo study.

Science.gov (United States)

Dietlein, T S; Jacobi, P C; Schröder, R; Krieglstein, G K

1997-05-01

Photoablative laser trabecular surgery has been proposed as an outflow-enhancing treatment for open-angle glaucoma. The aim of the study was to investigate the time course of repair response following low-thermal Erbium: YAG laser trabecular ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM) was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns) laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter) quartz fiber tip, the left unoperated eye served as control. At time intervals of 30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2 resulted in visible dissection of the ligamenta pectinata and reproducible microperforations of the TM exposing scleral tissue accompanied by blood reflux from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22 +/- 8 microns. At two days post-operative, ablation craters were still blood- and fibrin-filled. The inner surface of the craters were covered with granulocytes. No cellular infiltration of the collateral thermal damage zone was observed. At 10 days post-operative, progressive fibroblastic proliferation was observed, resulting in dense scar tissue formation with anterior synechiae, proliferating capillaries and loss of intertrabecular spaces inside the range of former laser treatment at 60 days post-operative. Trabecular microperforations were closed 60 days after laser treatment in all rabbits. IOP in treated and contralateral eyes did not significantly change its level during whole period of observation. Low-thermal infrared laser energy with minimal thermal damage to collateral

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

Science.gov (United States)

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.

Science.gov (United States)

Aruwajoye, Olumide O; Kim, Harry K W; Aswath, Pranesh B

2015-04-01

Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH. We hypothesized that the apatite composition changes in necrotic bone possibly contribute to increased osteoclast resorption and structural collapse of the femoral head. The purpose of this study was to assess the macroscopic and local phosphate composition of actively resorbed necrotic trabecular bone to isolate differences between areas of increased osteoclast resorption and normal bone formation. A piglet model of IOFH was used. Scanning electron microscopy (SEM), histology, X-ray absorbance near edge structure (XANES), and Raman spectroscopy were performed on femoral heads to characterize normal and necrotic trabecular bone. Backscattered SEM, micro-computed tomography and histology showed deformity and active resorption of necrotic bone compared to normal. XANES and Raman spectroscopy obtained from actively resorbed necrotic bone and normal bone showed increased carbonate-to-phosphate content in the necrotic bone. The changes in the apatite composition due to carbonate substitution may play a role in the increased resorption of necrotic bone due to its increase in solubility. Indeed, a better understanding of the apatite composition of necrotic bone could shed light on osteoclast activity and potentially improve therapeutic treatments that target excessive resorption of bone.

Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

Science.gov (United States)

McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2009-12-01

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

MRI of Mouse Models for Gliomas Shows Similarities to Humans and Can Be Used to Identify Mice for Preclinical Trials

Directory of Open Access Journals (Sweden)

Jason A. Koutcher

2002-01-01

Full Text Available Magnetic resonance imaging (MRI has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

Contribution of the endosteal surface of cortical bone to the trabecular pattern seen on IOPA radiographs: an in vitro study

Directory of Open Access Journals (Sweden)

P T Ravikumar

2012-01-01

Full Text Available Objectives: A study was conducted to assess the contribution of the cancellous and endosteal surface of the cortical bone to the trabecular pattern seen in an IOPA radiograph. Materials and methods: An in vitro study analyzing the contribution of the endosteal surface of cortical bone and cancellous bone to the trabecular pattern was conducted, using 60 specimens of desiccated human mandibles. The mode of execution involved IOPA radiographic evaluation of premolarmolar segments in the specimens before and after removal of cancellous bone. The radiographs were numbered for identification and subjected to evaluation by 5 dentomaxillofacial radiologists who were doubleblinded to ensure an unbiased interpretation. Results: The trabecular pattern appreciation by the experts in the IOPA radiographs before and after removal of cancellous bone displayed immaculate correlation as per the Goodman-Kruskal Gamma Coefficient values which was 0.78 indicating a very large correlation. The relative density of trabecular pattern was significantly higher in radiograph before than after removal of cancellous bone with p-value less than 0.05. Conclusion: Based on these results it was adjudged that both the cancellous and endosteal surface of cortical bone contributed significantly to the trabecular pattern in an IOPA radiograph.

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

Science.gov (United States)

Metcalf, Louis M; Dall'Ara, Enrico; Paggiosi, Margaret A; Rochester, John R; Vilayphiou, Nicolas; Kemp, Graham J; McCloskey, Eugene V

2018-01-01

Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TV d ); trabecular number, Tb.N; derived trabecular thickness, Tb.Th d ; derived trabecular spacing, Tb.Sp d ) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TV d was strongly correlated with micro-CT BV/TV (r 2 =0.95-0.98, RMSE=1%), but BV/TV d was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r 2 =0.61, RMSE=0.15mm -1 ). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm -1 ; r 2 =0.70-0.88, pmicrostructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time

The pattern of trabecular bone microarchitecture in the distal femur of typically developing children and its effect on processing of magnetic resonance images.

Science.gov (United States)

Modlesky, Christopher M; Whitney, Daniel G; Carter, Patrick T; Allerton, Brianne M; Kirby, Joshua T; Miller, Freeman

2014-03-01

Magnetic resonance imaging (MRI) is used to assess trabecular bone microarchitecture in humans; however, image processing can be labor intensive and time consuming. One aim of this study was to determine the pattern of trabecular bone microarchitecture in the distal femur of typically developing children. A second aim was to determine the proportion and location of magnetic resonance images that need to be processed to yield representative estimates of trabecular bone microarchitecture. Twenty-six high resolution magnetic resonance images were collected immediately above the growth plate in the distal femur of 6-12year-old typically developing children (n=40). Measures of trabecular bone microarchitecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the lateral aspect of the distal femur were determined using the twenty most central images (20IM). The average values for appBV/TV, appTb.N, appTb.Th and appTb.Sp from 20IM were compared to the average values from 10 images (10IM), 5 images (5IM) and 3 images (3IM) equally dispersed throughout the total image set and one image (1IM) from the center of the total image set using linear regression analysis. The resulting mathematical models were cross-validated using the leave-one-out technique. Distance from the growth plate was strongly and inversely related to appBV/TV (r(2)=0.68, p0.05). However, there was a progressive decrease in the strength of the relationships as a smaller proportion of images were used to predict estimates from 20IM (r(2)=0.98 to 0.99 using 10IM, 0.94 to 0.96 using 5IM, 0.87 to 0.90 using 3IM and 0.66 to 0.72 using 1IM; all pimage sets agreed extremely well with estimates from 20IM. The findings indicate that partial magnetic resonance image sets can be used to provide reasonable estimates of trabecular bone microarchitecture status in the distal femur of typically

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats

Science.gov (United States)

de Bakker, Chantal M. J.; Altman-Singles, Allison R.; Li, Yihan; Tseng, Wei-Ju; Li, Connie; Liu, X. Sherry

2017-01-01

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on post-menopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, while other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that while rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. PMID:28109138

Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous

DEFF Research Database (Denmark)

Ding, Ming; Hvid, I

2000-01-01

Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has...... traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial......, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allows...

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

Science.gov (United States)

Beresheim, Amy C; Pfeiffer, Susan K; Grynpas, Marc D; Alblas, Amanda

2018-02-07

The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals ( n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa. © 2018 Wiley Periodicals, Inc.

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

International Nuclear Information System (INIS)

Watanabe, Kenta; Hirata, Michiko; Tominari, Tsukasa; Matsumoto, Chiho; Endo, Yasuyuki; Murphy, Gillian; Nagase, Hideaki

2016-01-01

Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Kenta [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Hirata, Michiko [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Tominari, Tsukasa [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Matsumoto, Chiho [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Endo, Yasuyuki [Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, 981-8558 (Japan); Murphy, Gillian [Department of Oncology, University of Cambridge, Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE (United Kingdom); Nagase, Hideaki [Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY (United Kingdom); and others

2016-09-09

Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

Microfluidic enhancement of intramedullary pressure increases interstitial fluid flow and inhibits bone loss in hindlimb suspended mice.

Science.gov (United States)

Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

2010-08-01

Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process.

A theoretical framework for strain-related trabecular bone maintenance and adaptation

NARCIS (Netherlands)

Ruimerman, R.; Hilbers, P.A.J.; Rietbergen, van B.; Huiskes, R.

2005-01-01

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for

Capsid Mutated Adeno-Associated Virus Delivered to the Anterior Chamber Results in Efficient Transduction of Trabecular Meshwork in Mouse and Rat.

Directory of Open Access Journals (Sweden)

Barbara Bogner

Full Text Available Adeno associated virus (AAV is well known for its ability to deliver transgenes to retina and to mediate improvements in animal models and patients with inherited retinal disease. Although the field is less advanced, there is growing interest in AAV's ability to target cells of the anterior segment. The purpose of our study was to fully articulate a reliable and reproducible method for injecting the anterior chamber (AC of mice and rats and to investigate the transduction profiles of AAV2- and AAV8-based capsid mutants containing self-complementary (sc genomes in the anterior segment of the eye.AC injections were performed in C57BL/6 mice and Sprague Dawley rats. The cornea was punctured anterior of the iridocorneal angle. To seal the puncture site and to prevent reflux an air bubble was created in the AC. scAAVs expressing GFP were injected and transduction was evaluated by immunohistochemistry. Both parent serotype and capsid modifications affected expression. scAAV2- based vectors mediated efficient GFP-signal in the corneal endothelium, ciliary non-pigmented epithelium (NPE, iris and chamber angle including trabecular meshwork, with scAAV2(Y444F and scAAV2(triple being the most efficient.This is the first study to semi quantitatively evaluate transduction of anterior segment tissues following injection of capsid-mutated AAV vectors. scAAV2- based vectors transduced corneal endothelium, ciliary NPE, iris and trabecular meshwork more effectively than scAAV8-based vectors. Mutagenesis of surface-exposed tyrosine residues greatly enhanced transduction efficiency of scAAV2 in these tissues. The number of Y-F mutations was not directly proportional to transduction efficiency, however, suggesting that proteosomal avoidance alone may not be sufficient. These results are applicable to the development of targeted, gene-based strategies to investigate pathological processes of the anterior segment and may be applied toward the development of gene

Relationships between age and microarchitectural descriptors of iliac trabecular bone determined by microCT.

Science.gov (United States)

Deguette, C; Ramond-Roquin, A; Rougé-Maillart, C

2017-06-01

Estimation of age at death is a major issue in anthropology. The main anthropological histological methods propose studying the architecture of cortical bone. In bone histomorphometry, researches on metabolic bone diseases have provided normative tables for trabecular bone volume (BV/TV) according to age and gender of individuals on trans-iliac bone biopsies. We have used microCT, a non-destructive tool for measuring bone volume and trabecular descriptors to compare the French tables to a series of forensic anthropological population and if the two iliac bones could be used interchangeably. Coxal bone of a personal forensic collection whose age and gender were known (DNA identification) were used. Bone samples, centered on the same area than bone biopsy. MicroCT (pixel size: 36μm) was used to measure BV/TV and morphometric trabecular parameters of microarchitecture. An adjusted Z-score was calculated for BV/TV to compare with normative tables and a right/left comparison of trabecular parameters was provided. Twenty-seven iliac bones, which 20 forming 10 complete pelvises, aged between 24 and 73y.o. (average of 47.7 y.o.) were used. All adjusted Z-score were within normal values. There was a strong positive correlation between right and left sides for Tb.Th, Tb.N and Tb.Sp, but an insignificant correlation was obtained for BV/TV. Normative tables between age and BV/TV are valid and therefore usable in anthropology. They may represent an alternative to determine the age at death. Nevertheless, it requires a precise technique that could be a drawback in current practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Trabecular evidence for a human-like gait in Australopithecus africanus.

Directory of Open Access Journals (Sweden)

Meir M Barak

Full Text Available Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb.

Comparative Analysis of Bone Structural Parameters Reveals Subchondral Cortical Plate Resorption and Increased Trabecular Bone Remodeling in Human Facet Joint Osteoarthritis

Directory of Open Access Journals (Sweden)

Cordula Netzer

2018-03-01

Full Text Available Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15 and osteoarthritic (n = 22 lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.

Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

Directory of Open Access Journals (Sweden)

Zelieann R. Craig

2010-01-01

Full Text Available Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months C57BL/6Hsd female mice were divided into: CON (vehicle, VCD (160 mg/kg; 15d, or OVX (ovariectomized. Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05 than baseline, starting 1 month after ovarian failure in VCD and OVX mice. Following μCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.

Development of a mechanical testing and loading system for trabecular bone studies for long term culture

Directory of Open Access Journals (Sweden)

DB Jones

2003-03-01

Full Text Available A highly accurate (�3% mechanical loading and measurement system combined with a trabecular bone diffusion culture-loading chamber has been developed, which provides the ability to study trabecular bone (and possibly cartilage under controlled culture and loading conditions over long periods of time. The loading device has been designed to work in two main modes, either to apply a specific compressive strain to a trabecular bone cylinder or to apply a specific force and measure the resulting deformation. Presently, precisely machined bone cylinders can be loaded at frequencies between 0.1 Hz to 50 Hz and amplitudes over 7,000�e. The system allows accurate measurement of many mechanical properties of the tissue in real time, including visco-elastic properties. This paper describes the technical components, reproducibility, precision, and the calibration procedures of the loading system. Data on long term culture and mechanical responses to different loading patterns will be published separately.

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

Science.gov (United States)

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

Revision total knee arthroplasty with the use of trabecular metal cones

DEFF Research Database (Denmark)

Jensen, Claus L; Petersen, Michael Mygind; Schrøder, Henrik

2012-01-01

"Trabecular Metal Cone" (TM Cone) (Zimmer, Inc, Warsaw, Ind) for reconstruction of bone loss in the proximal tibia during revision total knee arthroplasty is now optional. Forty patients were randomized to receive revision total knee arthroplasty with or without TM Cone (No TM Cone). The Anderson...

Age-related changes of vertical and horizontal lumbar vertebral trabecular 3D bone microstructure is different in women and men.

Science.gov (United States)

Thomsen, Jesper Skovhus; Niklassen, Andreas Steenholt; Ebbesen, Ebbe Nils; Brüel, Annemarie

2013-11-01

The study presents a 3D method for subdividing a trabecular network into horizontal and vertical oriented bone. This method was used to investigate the age related changes of the bone volume fraction and thickness of horizontal and vertical trabeculae in human lumbar vertebral bone estimated with unbiased 3D methods in women and men over a large age-range. The study comprised second lumbar vertebral body bone samples from 40 women (aged 21.7-96.4years, median 56.6years) and 39 men (aged 22.6-94.6years, median 55.6years). The bone samples were μCT scanned and the 3D microstructure was quantified. A voxel based algorithm inspecting the local neighborhood is presented and used to segment the trabecular network into horizontal and vertical oriented bone. For both women and men BV/TV decreased significantly with age, Tb.Th* was independent of age, while SMI increased significantly with age. Vertical (BV.vert/TV) and horizontal (BV.horz/TV) bone volume fraction decreased significantly with age for both sexes. BV.vert/TV decreased significantly faster with age for women than for men. Vertical (Tb.Th*.vert) and horizontal (Tb.Th*.horz) trabecular thickness were independent of age, while Tb.Th*.horz/Tb.Th*.vert decreased significantly with age for both sexes. Additionally, the 95th percentile of the trabecular thickness distribution increased significantly with age for vertical trabeculae in women, whereas it was independent of age in men. In conclusion, we have shown that vertical and horizontal oriented bone density decreases with age in both women and men, and that vertical oriented bone is lost more quickly in women than in men. Furthermore, vertical and horizontal trabecular thickness were independent of age, whereas the horizontal to vertical trabecular thickness ratio decreased significantly with age indicating a relatively more pronounced thinning of horizontal trabeculae. Finally, the age-related loss of trabecular elements appeared to result in a compensatory

Comparison of different plasticity criteria for trabecular bone failure modelling

Czech Academy of Sciences Publication Activity Database

Jiroušek, Ondřej

2008-01-01

Roč. 8, č. 1 (2008), s. 10177-10178 ISSN 1617-7061. [Annual Meeting of International Association of Applied Mathematics and Mechanics. Bremen, 31.03.2008-04.04.2008] R&D Projects: GA ČR(CZ) GA103/05/1020 Institutional research plan: CEZ:AV0Z20710524 Keywords : nanoindentation * plasticity criteria * trabecular bone Subject RIV: FI - Traumatology, Orthopedics

FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.

Science.gov (United States)

Bornstein, Sheila; Brown, Sue A; Le, Phuong T; Wang, Xunde; DeMambro, Victoria; Horowitz, Mark C; MacDougald, Ormond; Baron, Roland; Lotinun, Sutada; Karsenty, Gerard; Wei, Wei; Ferron, Mathieu; Kovacs, Christopher S; Clemmons, David; Wan, Yihong; Rosen, Clifford J

2014-09-01

Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a

Impaired bone healing at tooth extraction sites in CD24-deficient mice: A pilot study.

Science.gov (United States)

Avivi-Arber, Limor; Avivi, Doran; Perez, Marilena; Arber, Nadir; Shapira, Shiran

2018-01-01

To use a micro-computed tomography (micro-CT) to quantify bone healing at maxillary first molar extraction sites, and test the hypothesis that bone healing is impaired in CD24-knockout mice as compared with wild-type C57BL/6J mice. Under ketamine-xylazine general anaesthesia, mice had either extraction of the right maxillary first molar tooth or sham operation. Mice were sacrificed 1 (n = 12/group), 2 (n = 6/group) or 4 (n = 6/group) weeks postoperatively. The right maxillae was disected. Micro-CT was used to quantify differences in bone microstructural features at extrction sites, between CD24-knockout mice and wild-type mice. CD24-Knockout mice displayed impaired bone healing at extraction sites that was manifested as decreased trabecular bone density, and decreased number and thickness of trabeculae. This pilot study suggests that CD24 plays an important role in extraction socket bone healing and may be used as a novel biomarker of bone quality and potential therapeutic target to improve bone healing and density following alveolar bone injury.

Trabecular bone structure and strength - remodelling and repair

DEFF Research Database (Denmark)

Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig

2000-01-01

vertical and horizontal struts reaching a certain magnitude and thereby inducing buckling under compression. 4) Microdamage and microfractures will occur - mainly in these very loaded vertical struts. The microfractures will be repaired by microcallus formation, and these calluses will later be removed...... can never be isolated in vivo, other factors need to be investigated: The interplay between the cortical shell and the trabecular network; transmission of load; the interplay between soft tissues (cartilage, connective tissue, muscle) and bone; the shock absorbing capacity of the discs...

Neocellularization and neovascularization of nanosized bioactive glass-coated decellularized trabecular bone scaffolds

KAUST Repository

Gerhardt, Lutz Christian; Widdows, Kate L.; Erol, Melek M.; Nandakumar, Anandkumar; Roqan, Iman S.; Ansari, Tahera I.; Boccaccini, Aldo R.

2012-01-01

amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm 2), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating

Direct mechanics assessment of elastic symmetries and properties of trabecular bone architecture

NARCIS (Netherlands)

Rietbergen, van B.; Odgaard, A.; Kabel, J.; Huiskes, H.W.J.

1996-01-01

A method is presented to find orthotropic elastic symmetries and constants directly from the elastic coefficients in the overall stiffness matrix of trabecular bone test specimens. Contrary to earlier developed techniques, this method does not require pure orthotropic behavior or additional fabric

Multi-axial fatigue of trabecular bone with respect to normal walking

CERN Document Server

Mostakhdemin, Mohammad; Syahrom, Ardiyansyah

2016-01-01

This book focuses on the analysis and treatment of osteoporotic bone based on drug administration, tracking fatigue behavior and taking into consideration the mechanical interaction of implants with trabecular bone. Weak trabeculae are one of the most important clinical features that need to be addressed in order to prevent hip joint fractures.

Relationship between tissue stiffness and degree of mineralization of developing trabecular bone

NARCIS (Netherlands)

Mulder, L.; Koolstra, J.H.; den Toonder, J.M.J.; van Eijden, T.M.G.J.

2008-01-01

It is unknown how the degree of mineralization of bone in individual trabecular elements is related to the corresponding mechanical properties at the bone tissue level. Understanding this relationship is important for the comprehension of the mechanical behavior of bone at both the apparent and

Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties

DEFF Research Database (Denmark)

Ding, Ming

2004-01-01

and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified...... matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes...... in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage. Udgivelsesdato: 2004 May...

A trabecular metal implant 4 months after placement: clinical-histologic case report.

Science.gov (United States)

Spinato, Sergio; Zaffe, Davide; Felice, Pietro; Checchi, Luigi; Wang, Hom-Lay

2014-02-01

The aim of this case report was to histologically evaluate the behavior of a trabecular metal (TM) implant composed of titanium and spatial 3-dimensional tantalum (Ta) trabeculae. This study is the first human histologic case report of this implant. A TM implant was placed in a 54-year-old woman exhibiting moderate chronic periodontitis. After periodontal treatment, the implant was inserted under favorable clinical conditions. Patient was not seen for 4 months because of unrelated breast reduction surgery. At the surgical reopening, periimplant inflammation affecting the coronal third of the implant was observed 4 months after implant placement. With patient's consent, the implant was removed for histologic analysis. Histology highlighted a greater amount of bone in close contact with Ta trabeculae than titanium surfaces. The finding of bone formation around the Ta trabeculae suggests that trabecular metal material promotes bone ingrowth for secondary implant stability. Additional evidence is needed to confirm this observation.

Characterization of synthetic foam structures used to manufacture artificial vertebral trabecular bone.

Science.gov (United States)

Fürst, David; Senck, Sascha; Hollensteiner, Marianne; Esterer, Benjamin; Augat, Peter; Eckstein, Felix; Schrempf, Andreas

2017-07-01

Artificial materials reflecting the mechanical properties of human bone are essential for valid and reliable implant testing and design. They also are of great benefit for realistic simulation of surgical procedures. The objective of this study was therefore to characterize two groups of self-developed synthetic foam structures by static compressive testing and by microcomputed tomography. Two mineral fillers and varying amounts of a blowing agent were used to create different expansion behavior of the synthetic open-cell foams. The resulting compressive and morphometric properties thus differed within and also slightly between both groups. Apart from the structural anisotropy, the compressive and morphometric properties of the synthetic foam materials were shown to mirror the respective characteristics of human vertebral trabecular bone in good approximation. In conclusion, the artificial materials created can be used to manufacture valid synthetic bones for surgical training. Further, they provide novel possibilities for studying the relationship between trabecular bone microstructure and biomechanical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

[Reproducibility and accuracy in the morphometric and mechanical quantification of trabecular bone from 3 Tesla magnetic resonance images].

Science.gov (United States)

Alberich-Bayarri, A; Martí-Bonmatí, L; Sanz-Requena, R; Sánchez-González, J; Hervás Briz, V; García-Martí, G; Pérez, M Á

2014-01-01

We used an animal model to analyze the reproducibility and accuracy of certain biomarkers of bone image quality in comparison to a gold standard of computed microtomography (μCT). We used magnetic resonance (MR) imaging and μCT to study the metaphyses of 5 sheep tibiae. The MR images (3 Teslas) were acquired with a T1-weighted gradient echo sequence and an isotropic spatial resolution of 180μm. The μCT images were acquired using a scanner with a spatial resolution of 7.5μm isotropic voxels. In the preparation of the images, we applied equalization, interpolation, and thresholding algorithms. In the quantitative analysis, we calculated the percentage of bone volume (BV/TV), the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp), the trabecular index (Tb.N), the 2D fractal dimension (D(2D)), the 3D fractal dimension (D(3D)), and the elastic module in the three spatial directions (Ex, Ey and Ez). The morphometric and mechanical quantification of trabecular bone by MR was very reproducible, with percentages of variation below 9% for all the parameters. Its accuracy compared to the gold standard (μCT) was high, with errors less than 15% for BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z. Our experimental results in animals confirm that the parameters of BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z obtained by MR have excellent reproducibility and accuracy and can be used as imaging biomarkers for the quality of trabecular bone. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

Science.gov (United States)

Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

2015-10-01

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P hyperthyroid mice (+50%, P hyperthyroid (P hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

Science.gov (United States)

Khorasani, Mohammad S; Diko, Sindi; Hsia, Allison W; Anderson, Matthew J; Genetos, Damian C; Haudenschild, Dominik R; Christiansen, Blaine A

2015-02-16

Previous studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury. Non-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption. μCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points. High-dose ALN treatment was able to prevent early trabecular

Marked disparity between trabecular and cortical bone loss with age in healthy men. Measurement by vertebral computed tomography and radial photon absorptiometry

International Nuclear Information System (INIS)

Meier, D.E.; Orwoll, E.S.; Jones, J.M.

1984-01-01

To define age-related changes in bone mineral content in normal men, we measured radial (proximal and distal) and vertebral bone mineral content in 62 men aged 30 to 92 years. Radial bone mineral content (largely cortical bone) was measured by single photon absorptiometry, and trabecular vertebral content (T12, L1 to L3) by computed tomography. Radial bone mineral content fell gradually (2% to 3.4% per decade) with age, but vertebral trabecular content fell more rapidly (12% per decade). Body size was not associated with the rate of bone loss from the distal radial and vertebral sites, but men with lower surface areas lost bone more rapidly at the predominantly cortical proximal radial site. The fact that radial cortical bone mineral content falls much less rapidly than vertebral trabecular content with age and is also associated with surface area indicates that trabecular and cortical bone compartments may be independently modulated. Age-related bone loss should not be considered a homogeneous process

Prediction of progression of radiographic knee osteoarthritis using tibial trabecular bone texture

DEFF Research Database (Denmark)

Woloszynski, T; Podsiadlo, P; Stachowiak, G W

2012-01-01

OBJECTIVE.: To develop a system for prediction of progression of radiographic knee osteoarthritis (OA) using tibial trabecular bone (TB) texture. METHODS.: We studied 203 knees with (n=68) or without (n=135) radiographic tibiofemoral OA in 105 subjects (90 men, 15 women, mean age 54 years) who ha...

Decreased trabecular bone biomechanical competence, apparent density, IGF-II and IGFBP-5 content in acromegaly

DEFF Research Database (Denmark)

Ueland, Thor; Ebbesen, Ebbe Nils; Thomsen, Jesper Skovhus

2002-01-01

of these growth factors in relation to biomechanical properties in acromegaly. MATERIALS AND METHODS: Trabecular bone biomechanical competence (compression test), apparent density (peripheral quantitative computed tomography, pQCT), and bone matrix contents of calcium (HCl hydrolysis) and IGFs (guanidinium......-HCl extraction) were measured in iliac crest biopsies from 13 patients with active acromegaly (two women and 11 men, aged 21-61 years) and 21 age- and sex-matched controls (four women and 17 men, aged 23-64 years). RESULTS: Trabecular bone pQCT was reduced in acromegalic patients compared with controls (P = 0...... bone content of IGF-I, IGFBP-3, or osteocalcin. However, IGF-II and IGFBP-5 content was decreased (P acromegaly, supporting previous observations...

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

OpenAIRE

Luca Giovanella; Fabrizio Fasolini; Sergio Suriano; Luca Mazzucchelli

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 9 9 m T c -pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissu...

Trabecular bone structural parameters evaluated using dental cone-beam computed tomography: cellular synthetic bones.

Science.gov (United States)

Ho, Jung-Ting; Wu, Jay; Huang, Heng-Li; Chen, Michael Y c; Fuh, Lih-Jyh; Hsu, Jui-Ting

2013-11-09

This study compared the adequacy of dental cone beam computed tomography (CBCT) and micro computed tomography (micro-CT) in evaluating the structural parameters of trabecular bones. The cellular synthetic bones in 4 density groups (Groups 1-4: 0.12, 0.16, 0.20, and 0.32 g/cm3) were used in this study. Each group comprised 8 experimental specimens that were approximately 1 cm3. Dental CBCT and micro-CT scans were conducted on each specimen to obtain independent measurements of the following 4 trabecular bone structural parameters: bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). Wilcoxon signed ranks tests were used to compare the measurement variations between the dental CBCT and micro-CT scans. A Spearman analysis was conducted to calculate the correlation coefficients (r) of the dental CBCT and micro-CT measurements. Of the 4 groups, the BV/TV and Tb.Th. measured using dental CBCT were larger compared with those measured using micro-CT. By contrast, the BS/BV measured using dental CBCT was significantly less compared with those measured using micro-CT. Furthermore, in the low-density groups (Groups 1 and 2), the Tb.Sp. measured using dental CBCT was smaller compared with those measured using micro-CT. However, the Tb.Sp. measured using dental CBCT was slightly larger in the high-density groups (Groups 3 and 4) than it was in the low density groups. The correlation coefficients between the BV/TV, BS/BV, Tb.Th., and Tb.Sp. values measured using dental CBCT and micro-CT were 0.9296 (p < .001), 0.8061 (p < .001), 0.9390 (p < .001), and 0.9583 (p < .001), respectively. Although the dental CBCT and micro-CT approaches exhibited high correlations, the absolute values of BV/TV, BS/BV, Tb.Th., Tb.Sp. differed significantly between these measurements. Additional studies must be conducted to evaluate using dental CBCT in clinical practice.

The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

Science.gov (United States)

2016-01-01

Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (Pmicro-CT and CBCT (Pimplant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

Science.gov (United States)

Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

2011-03-01

Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

Relationship of bony trabecular characteristics and age to bone mass

International Nuclear Information System (INIS)

Choi, Dong Hoon; Song, Young Han; Yoon, Young Nam; Lee, Wan; Lee, Byung Do

2006-01-01

Bony strength is dependent on bone mass and bony structure. So this study was designed to investigate the relationship between the bone mass and bony mass and bony trabecular characteristics. Study subjects were 51 females (average age 68.6 years) and 20 males (average age 66.4 years). Bony mineral density (BMD, grams/cm 2 ) of proximal femur was measured by a dual energy X-ray absorptiometry (DEXA). Regions of interest (ROIs) were selected from the digitized radiographs of proximal femur. A customized computer program processed morphologic operations (MO) of ROIs. 44 skeletal variables of MO were calculated from ROIs on the Ward's triangle and greater trochanter of femur. WHO BMD classes were predicted by MO variables of the same ROI. Classification and Regression Tree analysis was used for calculating weighted kappa values, sensitivity and specificity of MO. The discriminating factors of morphologic operation were branch point, branch point [per cm sq]. Age also played important role in distinguishing osteoporotic classes. The sensitivity of MO at Ward's triangle and Greater Trochanter was 91.8%, 65.6%, respectively. The specificity of MO was 100% at Ward's triangle and Greater Trochanter. Bony trabecular characteristics obtained using radiological bone morphometric analysis seem to be related to bone mass

Hilar cholangiocarcinoma is pathologically similar to pancreatic duct adenocarcinoma: suggestions of similar background and development.

Science.gov (United States)

Nakanuma, Yasuni; Sato, Yasunori

2014-07-01

Routine experiences suggest that cholangiocarcinomas (CCAs) show different clinicopathological behaviors along the biliary tree, and hilar CCA apparently resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for these similarities were reviewed. While all cases of PDAC, hilar CCA, intrahepatic CCA (ICCA) and CCA components of combined hepatocellular-cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular components and cuboidal carcinoma cells were common in ICCA and CCA components of cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA, although their expression was rare and mild in CCA components in cHC-CCA and ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA components of cHC-CCA but have a similar development to PDAC. These similarities may be explained by the unique anatomical, embryological and reactive nature of the pancreatobiliary tract. Further studies of these intractable malignancies are warranted. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Characterizing trabecular bone structure for assessing vertebral fracture risk on volumetric quantitative computed tomography

Science.gov (United States)

Nagarajan, Mahesh B.; Checefsky, Walter A.; Abidin, Anas Z.; Tsai, Halley; Wang, Xixi; Hobbs, Susan K.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

2015-03-01

While the proximal femur is preferred for measuring bone mineral density (BMD) in fracture risk estimation, the introduction of volumetric quantitative computed tomography has revealed stronger associations between BMD and spinal fracture status. In this study, we propose to capture properties of trabecular bone structure in spinal vertebrae with advanced second-order statistical features for purposes of fracture risk assessment. For this purpose, axial multi-detector CT (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. A semi-automated method was used to annotate the trabecular compartment in the central vertebral slice with a circular region of interest (ROI) to exclude cortical bone; pixels within were converted to values indicative of BMD. Six second-order statistical features derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the ROI were then extracted and used in conjunction with a generalized radial basis functions (GRBF) neural network to predict the failure load of the specimens; true failure load was measured through biomechanical testing. Prediction performance was evaluated with a root-mean-square error (RMSE) metric. The best prediction performance was observed with GLCM feature `correlation' (RMSE = 1.02 ± 0.18), which significantly outperformed all other GLCM features (p biomechanical strength prediction in spinal vertebrae can be significantly improved through characterization of trabecular bone structure with GLCM-derived texture features.

Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone – An experimental and finite element study

DEFF Research Database (Denmark)

Ojanen, X.; Tanska, P.; Malo, M. K.H.

2017-01-01

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n = 11, male, age 18–78 years) from 11 proximal femurs were charact......). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone....

Ethnic differences in trabecular meshwork height by optical coherence tomography.

Science.gov (United States)

Chen, Rebecca I; Barbosa, Diego T; Hsu, Chi-Hsin; Porco, Travis C; Lin, Shan C

2015-04-01

Differences in ocular anatomy may contribute to ethnic differences in glaucoma risk. Because the trabecular meshwork (TM) plays an important role in aqueous outflow, its anatomy in relation to at-risk populations may provide insight into a potential contributor to elevated intraocular pressure and thus to probability of glaucoma development. To investigate whether differences exist in TM height between ethnic groups. This prospective study took place from January 1, 2012, to December 31, 2013. Adult patients who self-reported as being of white, Asian, Hispanic, or African American ethnicity were recruited from ophthalmology clinics at the University of California, San Francisco. The TM height was assessed using spectral-domain anterior segment optical coherence tomography. Trabecular meshwork height was measured from the scleral spur to the Schwalbe line. We hypothesized that ethnicities with a higher prevalence of glaucoma would tend to have shorter TM heights. We collected data from 460 eyes of 291 participants after excluding 34 optical coherence tomographic scans owing to poor image quality. The final sample was 32.2% white, 45.1% Asian, 10.5% African American, and 12.1% Hispanic. There were 64.2% women, and the mean age was 68.1 years. The mean (SD) TM height among all eyes included in the study was 836 (131) μm. The mean (SD) TM height was characterized among white (851 [131] μm), Asian (843 [126] μm), Hispanic (822 [147] μm), and African American (771 [118] μm) persons. Ethnicity was not associated with TM height overall (P = .23, linear mixed regression model). However, the TM heights of African American participants (771 μm) were shorter than those of white (851 μm; adjusted difference 95% CI, -119.8 to -8.1; P = .02) and Asian (843 μm; adjusted difference 95% CI, -117.4 to -10.8; P = .02) participants. Although TM height is not associated with ethnicity overall, African American individuals have shorter TM heights compared with Asian and white

Fabrication of Trabecular Bone-Templated Tissue-Engineered Constructs by 3D Inkjet Printing.

Science.gov (United States)

Vanderburgh, Joseph P; Fernando, Shanik J; Merkel, Alyssa R; Sterling, Julie A; Guelcher, Scott A

2017-11-01

3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

Directory of Open Access Journals (Sweden)

Tommy Noh

Full Text Available We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/- females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR (tfm mutants. The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/- female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.

Automatic analysis of trabecular bone structure from knee MRI

DEFF Research Database (Denmark)

Marques, Joselene; Granlund, Rabia; Lillholm, Martin

2012-01-01

We investigated the feasibility of quantifying osteoarthritis (OA) by analysis of the trabecular bone structure in low-field knee MRI. Generic texture features were extracted from the images and subsequently selected by sequential floating forward selection (SFFS), following a fully automatic......, uncommitted machine-learning based framework. Six different classifiers were evaluated in cross-validation schemes and the results showed that the presence of OA can be quantified by a bone structure marker. The performance of the developed marker reached a generalization area-under-the-ROC (AUC) of 0...

Trabecular metal acetabular components in primary total hip arthroplasty

DEFF Research Database (Denmark)

Laaksonen, Inari; Lorimer, Michelle; Gromov, Kirill

2018-01-01

Background and purpose - Trabecular metal (TM) cups have demonstrated favorable results in acetabular revision and their use in primary total hip arthroplasty (THA) is increasing. Some evidence show that TM cups might decrease periprosthetic infection (PPI) incidence. We compared the survivorship...... of TM cups with that of other uncemented cups in primary THA, and evaluated whether the use of TM cups is associated with a lower risk of PPI. Patients and methods - 10,113 primary THAs with TM cup and 85,596 THAs with other uncemented cups from 2 high-quality national arthroplasty registries were...

Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Science.gov (United States)

Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

2013-01-01

Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

The effect of an osteolytic tumor on the three-dimensional trabecular bone morphology in an animal model

International Nuclear Information System (INIS)

Kurth, A.A.; Mueller, R.

2001-01-01

Objective. To investigate the application of micro-computed tomography (μCT) for the assessment of density differences and deterioration of three-dimensional architecture of trabecular bone in an experimental rat model for tumor- induced osteolytic defects.Design and materials. Walker carcinosarcoma 256 malignant breast cancer cells (W256) were surgically implanted into the medullary canal of the left femur of 15 4-month-old rats. Twenty-eight days after surgery all animals were killed and both femora from each rat were harvested. A total of 30 specimens (left and right femur) were scanned in a desk-top μCT imaging system (μCT 20, Scanco Medical) to assess densitometric and architectural parameters. For each specimen a total of 200 micro-tomographic slices with a resolution of 30 μm in the distal metaphysis was taken. Bone mineral content (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for trabecular bone only (tBMC). Architectural indices (BV/TV, Tb.N, Tb.Th, Tb.Sp) according to standard definitions used in histomorphometry were calculated for trabecular bone.Results. The quantitative analysis of density parameters revealed significantly (P<0.001) lower values for ctBMC and tBMC in the tumor-bearing group (T) of 26% and 31%, respectively, compared with the contralateral control group. The quantitative analysis revealed significant (P<0.001) changes in the architectural parameters in the tumor-bearing bones compared with the contralateral control group: BV/TV was 30% lower, Tb.N and BS/TV decreased by 24% and 21%, respectively, Tb.Th. decreased by 10% and Tb.Sp. increased by 94%.Conclusions. This study demonstrates that μCT is able to provide three-dimensional parameters of bone mass and trabecular structure in an animal model for tumor-induced bone loss. Recent advances in therapeutic approaches for skeletal diseases such as osteoporosis and metastatic bone disease rely on an understanding of the effects of the agents on the mechanical

[Histological structure of the trabecular meshwork in the eyeball: challenging the traditional concept and preliminary findings in rabbits, rats and mice].

Science.gov (United States)

Shi, Yun; Zhou, Fan-Qi; Luo, Zhou-Cai; Chen, Ying-Hua; Chen, Yu; Dong, Wei-Ren

2017-10-20

To verify that the trabecular meshwork (TM) in the wall of the eyeball consists of smooth muscle fibers instead of collagen fibers or endothelial cells. Eighteen fresh eyeballs from 3 rabbits, 3 SD rats and 3 mice were sectioned along the sagittal plane and sliced after paraffin embedding for HE staining, VG staining, Masson staining, α-SMA immunohistochemistry or CD31 immunohistochemistry. These slices were observed under microscope and the structure of the TM was compared with those of scleral collagen fibers, ciliary muscles and endothelial cells. HE staining of the eyeball slices from the 3 animal species resulted in purplish red staining of the TM, which was highly consistent with ciliary muscle fibers. The cell?like structures on the surface of the TM were not clearly outlined, with flat nuclei showing a dark purple staining; these structures did not show obvious boundaries from the TM. Ciliary muscle fibers, which were smooth muscle cells in nature, were aligned in bundles in various directions. The longitudinally sectioned cells were flat and contained purplish cytoplasm and highly flattened nuclei. Scleral collagen fibers were stained dark red with a few fibroblasts sandwiched among them. The long axis of the fibroblasts was in parallel with that of the collagen fibers. The outline of the fibroblast was not clear and the nucleus was flat in dark blue. The vascular endothelial cells presented with different morphologies and contained light purplish cytoplasm and dark nuclei, protruding into the vascular cavity. VG staining of the TM revealed a pale red filamentous structure, and the collagen fibers were stained bright red. Masson staining of the TM showed a reticular structure consisting mainly of dark red fibers intermingled with thin green fibers. Scleral collagen fibers presented with a cord?like green wavy structure. The endothelial cells were green and flat, while the ciliary smooth muscle fibers were purple. In immunohistochemistry for α?SMA, the TM

Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

Directory of Open Access Journals (Sweden)

Hen-Yu Liu

2013-01-01

Full Text Available The aim of this study is to examine the therapeutic potential of deep sea water (DSW on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8 and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP. Deep sea water at hardness (HD 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3 by MTT assay. For in vivo animal study, bone mineral density (BMD was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM.

Mechanical and morphological properties of trabecular bone samples obtained from third metacarpal bones of cadavers of horses with a bone fragility syndrome and horses unaffected by that syndrome.

Science.gov (United States)

Symons, Jennifer E; Entwistle, Rachel C; Arens, Amanda M; Garcia, Tanya C; Christiansen, Blaine A; Fyhrie, David P; Stover, Susan M

2012-11-01

To determine morphological and mechanical properties of trabecular bone of horses with a bone fragility syndrome (BFS; including silicate-associated osteoporosis). Cylindrical trabecular bone samples from the distal aspects of cadaveric third metacarpal bones of 39 horses (19 horses with a BFS [BFS bone samples] and 20 horses without a BFS [control bone samples]). Bone samples were imaged via micro-CT for determination of bone volume fraction; apparent and mean mineralized bone densities; and trabecular number, thickness, and separation. Bone samples were compressed to failure for determination of apparent elastic modulus and stresses, strains, and strain energy densities for yield, ultimate, and failure loads. Effects of BFS and age of horses on variables were determined. BFS bone samples had 25% lower bone volume fraction, 28% lower apparent density, 18% lower trabecular number and thickness, and 16% greater trabecular separation versus control bone samples. The BFS bone samples had 22% lower apparent modulus and 32% to 33% lower stresses, 10% to 18% lower strains, and 41 % to 52% lower strain energy densities at yield, ultimate, and failure loads, compared with control bone samples. Differences between groups of bone samples were not detected for mean mineral density and trabecular anisotropy. Results suggested that horses with a BFS had osteopenia and compromised trabecular bone function, consistent with bone deformation and pathological fractures that develop in affected horses. Effects of this BFS may be systemic, and bones other than those that are clinically affected had changes in morphological and mechanical properties.

Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats.

Science.gov (United States)

Ju, Yong-In; Sone, Teruki; Ohnaru, Kazuhiro; Tanaka, Kensuke; Fukunaga, Masao

2015-11-01

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis. Copyright © 2015 the American Physiological Society.

Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice

Directory of Open Access Journals (Sweden)

Qingtao Liu

2016-11-01

Full Text Available H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06 virus was highly pathogenic for mice, with a 50% mouse lethal dose of 102.83 50% egg infectious dose, whereas the A/duck/Nanjing/01/1999 (NJ01 virus was low pathogenic for mice, with a 50% mouse lethal dose of >106.81 50% egg infectious dose. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only twelve different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.

Strain analysis of trabecular bone using time-resolved X-ray microtomography

Czech Academy of Sciences Publication Activity Database

Jiroušek, Ondřej; Zlámal, Petr; Kytýř, Daniel; Kroupa, M.

2011-01-01

Roč. 633, Suppl. 1 (2011), s. 148-151 ISSN 0168-9002. [International Workshop on Radiation Imaging Detectors /11./. Praha, 28.06.2009-02.07.2009] R&D Projects: GA ČR(CZ) GP103/07/P483 Institutional research plan: CEZ:AV0Z20710524 Keywords : trabecular bone * X-ray microtomography * strain analysis * intrinsic material properties Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 1.207, year: 2011

Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

Science.gov (United States)

Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading

Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

Directory of Open Access Journals (Sweden)

Ronald Y Kwon

Full Text Available Interstitial fluid flow (IFF is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of

Transgenic Expression of Dspp Partially Rescued the Long Bone Defects of Dmp1-null Mice

Science.gov (United States)

Jani, Priyam H.; Gibson, Monica P.; Liu, Chao; Zhang, Hua; Wang, Xiaofang; Lu, Yongbo; Qin, Chunlin

2016-01-01

Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that

A novel use of 3D printing model demonstrates the effects of deteriorated trabecular bone structure on bone stiffness and strength.

Science.gov (United States)

Barak, Meir Max; Black, Margaret Arielle

2018-02-01

Trabecular bone structure is crucial to normal mechanical behavior of bones. Studies have shown that osteoporosis negatively affects trabecular bone structure, mainly by reducing bone volume fraction (BV/TV) and thus increasing fracture risk. One major limitation in assessing and quantifying the effect of this structural deterioration is that no two trabecular structures are identical. Thus, when we compare a group of healthy bones against a different group of bones that experienced resorption (i.e. decreased BV/TV) we only discover an "average" mechanical effect. It is impossible to quantify the mechanical effect of individual structural deterioration for each sample, simply because we never have the same sample in both states (intact and deteriorated structure). 3D printing is a new technology that can assist in overcoming this issue. Here we report a preliminary study that compares a healthy 3D printed trabecular bone model with the same model after bone resorption was simulated. Since the deteriorated structural bone model is derived from the healthy one, it is possible to directly estimate (percentage wise) the decrease of tissue stiffness and strength as a result of bone resorption for this specific structure. Our results demonstrate that a relatively small decrease in BV/TV (about 8%) leads to a dramatic decrease in structural strength (24%) and structural stiffness (17%), (P printing is a novel and valuable tool for quantifying the effect of structural deterioration on the mechanical properties of trabecular bone. In the future, this approach may help us attain better personal fracture risk assessments by CT scanning, 3D printing and mechanically testing individual bone replicas from patients suffering excessive bone resorption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trabecular architecture of the manual elements reflects locomotor patterns in primates.

Science.gov (United States)

Matarazzo, Stacey A

2015-01-01

The morphology of trabecular bone has proven sensitive to loading patterns in the long bones and metacarpal heads of primates. It is expected that we should also see differences in the manual digits of primates that practice different methods of locomotion. Primate proximal and middle phalanges are load-bearing elements that are held in different postures and experience different mechanical strains during suspension, quadrupedalism, and knuckle walking. Micro CT scans of the middle phalanx, proximal phalanx and the metacarpal head of the third ray were used to examine the pattern of trabecular orientation in Pan, Gorilla, Pongo, Hylobates and Macaca. Several zones, i.e., the proximal ends of both phalanges and the metacarpal heads, were capable of distinguishing between knuckle-walking, quadrupedal, and suspensory primates. Orientation and shape seem to be the primary distinguishing factors but differences in bone volume, isotropy index, and degree of anisotropy were seen across included taxa. Suspensory primates show primarily proximodistal alignment in all zones, and quadrupeds more palmar-dorsal orientation in several zones. Knuckle walkers are characterized by having proximodistal alignment in the proximal ends of the phalanges and a palmar-dorsal alignment in the distal ends and metacarpal heads. These structural differences may be used to infer locmotor propensities of extinct primate taxa.

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

Science.gov (United States)

Portal-Núñez, Sergio; Murillo-Cuesta, Silvia; Lozano, Daniel; Cediel, Rafael; Esbrit, Pedro

2014-01-01

Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone. PMID:24503961

Assessing vertebral fracture risk on volumetric quantitative computed tomography by geometric characterization of trabecular bone structure

Science.gov (United States)

Checefsky, Walter A.; Abidin, Anas Z.; Nagarajan, Mahesh B.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

2016-03-01

The current clinical standard for measuring Bone Mineral Density (BMD) is dual X-ray absorptiometry, however more recently BMD derived from volumetric quantitative computed tomography has been shown to demonstrate a high association with spinal fracture susceptibility. In this study, we propose a method of fracture risk assessment using structural properties of trabecular bone in spinal vertebrae. Experimental data was acquired via axial multi-detector CT (MDCT) from 12 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. Common image processing methods were used to annotate the trabecular compartment in the vertebral slices creating a circular region of interest (ROI) that excluded cortical bone for each slice. The pixels inside the ROI were converted to values indicative of BMD. High dimensional geometrical features were derived using the scaling index method (SIM) at different radii and scaling factors (SF). The mean BMD values within the ROI were then extracted and used in conjunction with a support vector machine to predict the failure load of the specimens. Prediction performance was measured using the root-mean-square error (RMSE) metric and determined that SIM combined with mean BMD features (RMSE = 0.82 +/- 0.37) outperformed MDCT-measured mean BMD (RMSE = 1.11 +/- 0.33) (p biomechanical strength prediction in vertebrae can be significantly improved through the use of SIM-derived texture features from trabecular bone.

Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

Science.gov (United States)

Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

2010-01-01

Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.

Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

Science.gov (United States)

Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

2014-08-01

Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc.

Development and initial validation of a novel smoothed-particle hydrodynamics-based simulation model of trabecular bone penetration by metallic implants.

Science.gov (United States)

Kulper, Sloan A; Fang, Christian X; Ren, Xiaodan; Guo, Margaret; Sze, Kam Y; Leung, Frankie K L; Lu, William W

2018-04-01

A novel computational model of implant migration in trabecular bone was developed using smoothed-particle hydrodynamics (SPH), and an initial validation was performed via correlation with experimental data. Six fresh-frozen human cadaveric specimens measuring 10 × 10 × 20 mm were extracted from the proximal femurs of female donors (mean age of 82 years, range 75-90, BV/TV ratios between 17.88% and 30.49%). These specimens were then penetrated under axial loading to a depth of 10 mm with 5 mm diameter cylindrical indenters bearing either flat or sharp/conical tip designs similar to blunt and self-tapping cancellous screws, assigned in a random manner. SPH models were constructed based on microCT scans (17.33 µm) of the cadaveric specimens. Two initial specimens were used for calibration of material model parameters. The remaining four specimens were then simulated in silico using identical material model parameters. Peak forces varied between 92.0 and 365.0 N in the experiments, and 115.5-352.2 N in the SPH simulations. The concordance correlation coefficient between experimental and simulated pairs was 0.888, with a 95%CI of 0.8832-0.8926, a Pearson ρ (precision) value of 0.9396, and a bias correction factor Cb (accuracy) value of 0.945. Patterns of bone compaction were qualitatively similar; both experimental and simulated flat-tipped indenters produced dense regions of compacted material adjacent to the advancing face of the indenter, while sharp-tipped indenters deposited compacted material along their peripheries. Simulations based on SPH can produce accurate predictions of trabecular bone penetration that are useful for characterizing implant performance under high-strain loading conditions. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1114-1123, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A computer-aided system for automatic extraction of femur neck trabecular bone architecture using isotropic volume construction from clinical hip computed tomography images.

Science.gov (United States)

Vivekanandhan, Sapthagirivasan; Subramaniam, Janarthanam; Mariamichael, Anburajan

2016-10-01

Hip fractures due to osteoporosis are increasing progressively across the globe. It is also difficult for those fractured patients to undergo dual-energy X-ray absorptiometry scans due to its complicated protocol and its associated cost. The utilisation of computed tomography for the fracture treatment has become common in the clinical practice. It would be helpful for orthopaedic clinicians, if they could get some additional information related to bone strength for better treatment planning. The aim of our study was to develop an automated system to segment the femoral neck region, extract the cortical and trabecular bone parameters, and assess the bone strength using an isotropic volume construction from clinical computed tomography images. The right hip computed tomography and right femur dual-energy X-ray absorptiometry measurements were taken from 50 south-Indian females aged 30-80 years. Each computed tomography image volume was re-constructed to form isotropic volumes. An automated system by incorporating active contour models was used to segment the neck region. A minimum distance boundary method was applied to isolate the cortical and trabecular bone components. The trabecular bone was enhanced and segmented using trabecular enrichment approach. The cortical and trabecular bone features were extracted and statistically compared with dual-energy X-ray absorptiometry measured femur neck bone mineral density. The extracted bone measures demonstrated a significant correlation with neck bone mineral density (r > 0.7, p computed tomography images scanned with low dose could eventually be helpful in osteoporosis diagnosis and its treatment planning. © IMechE 2016.

Serial analysis of gene expression (SAGE) in normal human trabecular meshwork.

Science.gov (United States)

Liu, Yutao; Munro, Drew; Layfield, David; Dellinger, Andrew; Walter, Jeffrey; Peterson, Katherine; Rickman, Catherine Bowes; Allingham, R Rand; Hauser, Michael A

2011-04-08

To identify the genes expressed in normal human trabecular meshwork tissue, a tissue critical to the pathogenesis of glaucoma. Total RNA was extracted from human trabecular meshwork (HTM) harvested from 3 different donors. Extracted RNA was used to synthesize individual SAGE (serial analysis of gene expression) libraries using the I-SAGE Long kit from Invitrogen. Libraries were analyzed using SAGE 2000 software to extract the 17 base pair sequence tags. The extracted sequence tags were mapped to the genome using SAGE Genie map. A total of 298,834 SAGE tags were identified from all HTM libraries (96,842, 88,126, and 113,866 tags, respectively). Collectively, there were 107,325 unique tags. There were 10,329 unique tags with a minimum of 2 counts from a single library. These tags were mapped to known unique Unigene clusters. Approximately 29% of the tags (orphan tags) did not map to a known Unigene cluster. Thirteen percent of the tags mapped to at least 2 Unigene clusters. Sequence tags from many glaucoma-related genes, including myocilin, optineurin, and WD repeat domain 36, were identified. This is the first time SAGE analysis has been used to characterize the gene expression profile in normal HTM. SAGE analysis provides an unbiased sampling of gene expression of the target tissue. These data will provide new and valuable information to improve understanding of the biology of human aqueous outflow.

Vertebral body bone strength: the contribution of individual trabecular element morphology.

Science.gov (United States)

Parkinson, I H; Badiei, A; Stauber, M; Codrington, J; Müller, R; Fazzalari, N L

2012-07-01

Although the amount of bone explains the largest amount of variability in bone strength, there is still a significant proportion unaccounted for. The morphology of individual bone trabeculae explains a further proportion of the variability in bone strength and bone elements that contribute to bone strength depending on the direction of loading. Micro-CT imaging enables measurement of bone microarchitecture and subsequently mechanical strength of the same sample. It is possible using micro-CT data to perform morphometric analysis on individual rod and plate bone trabeculae using a volumetric spatial decomposition algorithm and hence determine their contribution to bone strength. Twelve pairs of vertebral bodies (T12/L1 or L4/L5) were harvested from human cadavers, and bone cubes (10 × 10 × 10 mm) were obtained. After micro-CT imaging, a volumetric spatial decomposition algorithm was applied, and measures of individual trabecular elements were obtained. Bone strength was measured in compression, where one bone specimen from each vertebral segment was tested supero-inferiorly (SI) and the paired specimen was tested antero-posteriorly (AP). Bone volume fraction was the strongest individual determinant of SI strength (r(2) = 0.77, p body bone architecture into its constituent morphological elements shows that trabecular element morphology has specific functional roles to assist in maintaining skeletal integrity.

Chronic psychosocial stress disturbs long-bone growth in adolescent mice

Directory of Open Access Journals (Sweden)

Sandra Foertsch

2017-12-01

Full Text Available Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelationship between mental and skeletal health. Although depressive disorders have been shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD patients is less consistent. Therefore, the present study investigated the influence of chronic psychosocial stress on bone using a well-established murine model for PTSD. C57BL/6N mice (7 weeks old were subjected to chronic subordinate colony housing (CSC for 19 days, whereas control mice were singly housed. Anxiety-related behavior was assessed in the open-field/novel-object test, after which the mice were euthanized to assess endocrine and bone parameters. CSC mice exhibited increased anxiety-related behavior in the open-field/novel-object test, increased adrenal and decreased thymus weights, and unaffected plasma morning corticosterone. Microcomputed tomography and histomorphometrical analyses revealed significantly reduced tibia and femur lengths, increased growth-plate thickness and reduced mineral deposition at the growth plate, suggesting disturbed endochondral ossification during long-bone growth. This was associated with reduced Runx2 expression in hypertrophic chondrocytes in the growth plate. Trabecular thicknesses and bone mineral density were significantly increased in CSC compared to singly housed mice. Tyrosine hydroxylase expression was increased in bone marrow cells located at the growth plates of CSC mice, implying that local adrenergic signaling might be involved in the effects of CSC on the skeletal phenotype. In conclusion, chronic psychosocial stress negatively impacts endochondral ossification in the growth plate, affecting both longitudinal and appositional bone growth in adolescent mice.

Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

Science.gov (United States)

Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of a measuring technique with computed tomography for cement penetration into trabecular bone underneath the tibial tray in total knee arthroplasty on a cadaver model

International Nuclear Information System (INIS)

Verburg, Hennie; Ridder, Laurens C van de; Verhoeven, Vincent WJ; Pilot, Peter

2014-01-01

In total knee arthroplasty (TKA), cement penetration between 3 and 5 mm beneath the tibial tray is required to prevent loosening of the tibia component. The objective of this study was to develop and validate a reliable in vivo measuring technique using CT imaging to assess cement distribution and penetration depth in the total area underneath a tibia prosthesis. We defined the radiodensity ranges for trabecular tibia bone, polymethylmethacrylate (PMMA) cement and cement-penetrated trabecular bone and measured the percentages of cement penetration at various depths after cementing two tibia prostheses onto redundant femoral heads. One prosthesis was subsequently removed to examine the influence of the metal tibia prostheses on the quality of the CT images. The percentages of cement penetration in the CT slices were compared with percentages measured with photographs of the corresponding transversal slices. Trabecular bone and cement-penetrated trabecular bone had no overlap in quantitative scale of radio-density. There was no significant difference in mean HU values when measuring with or without the tibia prosthesis. The percentages of measured cement-penetrated trabecular bone in the CT slices of the specimen were within the range of percentages that could be expected based on the measurements with the photographs (p = 0.04). CT scan images provide valid results in measuring the penetration and distribution of cement into trabecular bone underneath the tibia component of a TKA. Since the proposed method does not turn metal elements into artefacts, it enables clinicians to assess the width and density of the cement mantle in vivo and to compare the results of different cementing methods in TKA

Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

Science.gov (United States)

Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

2016-10-01

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

Science.gov (United States)

Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; Van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

2016-01-01

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging. PMID:27759061

Preliminary report of cells at risk at the bone surface in trabecular bone

International Nuclear Information System (INIS)

Jee, W.S.S.; Wronski, T.J.; Kimmel, D.B.; Dell, R.B.; Johnson, F.

1975-01-01

This is a report of some early work on the cells at risk portion of the dynamic microanatomical dosimetry program of the Bone Group. The cells lining the trabecular bone of thoracic vertebral bodies from beagles aged 568, 2942, 4117, 4277, 4629, and 4801 days were characterized. Histologic and sampling experience gained in this attempt indicates that further improvements are needed

Methanol Extract of Euchelus asper Prevents Bone Resorption in Ovariectomised Mice Model

Directory of Open Access Journals (Sweden)

Babita Balakrishnan

2014-01-01

Full Text Available Marine molluscs are widely distributed throughout the world and many bioactive compounds exhibiting antiviral, antitumor, antileukemic, and antibacterial activity have been reported worldwide. The present study was designed to investigate the beneficial effect of methanol extract of Euchelus asper (EAME on estrogen deficiency induced osteoporosis in ovariectomised mice model. Forty-two female Swiss albino mice were randomly assigned into Sham operated (Sham group and six ovariectomised (OVX subgroups such as OVX with vehicle (OVX; OVX with estradiol (2 mg/kg/day; OVX with EAME of graded doses (25, 50, 100, and 200 mg/kg/day. Bone turnover markers like serum alkaline phosphatase (ALP, serum acid phosphatase (ACP, serum calcium, and histological investigations of tibia and uterus were analysed. Metaphyseal DNA content of the femur bone was also studied. Antiosteoclastogenic activity of EAME was examined. Administration of EAME was able to reduce the increased bone turnover markers in the ovariectomised mice. Histomorphometric analysis revealed an increase in bone trabeculation and restoration of trabecular separation by EAME treatment. Metaphyseal DNA content of the femur of the OVX mice was increased by EAME administration. EAME also showed a potent antiosteoclastogenic behaviour. Thus, the present study reveals that EAME was able to successfully reduce the estrogen deficiency induced bone loss.

Bone dosimetry using synthetic images to represent trabecular bones of five regions of the human body

Energy Technology Data Exchange (ETDEWEB)

Lima Filho, Jose de M. [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Recife, PE (Brazil); Vieira, Jose W. [Escola Politecnica de Pernambuco (POLI). Universidade de Pernambuco (UPE), Recife, PE (Brazil); Lima, Vanildo J. de M., E-mail: vjr@ufpe.br [Departamento de Anatomia. Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Lima, Lindeval F., E-mail: lindeval@dmat.ufrr.br [Departamento de Matematica (DMAT). Universidade Federal de Roraima (UFRR), Boa Vista, RR (Brazil); Lima, Fernando R.A., E-mail: falima@cnen.gov.br [Centro Regional de Ciencias Nucleares (CRCN/NE-CNEN-PE), Recife, PE (Brazil); Vasconcelos, Wagner E. de [Departamento de Energia Nuclear (DEN). Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

2011-07-01

One of the greatest challenges in numerical dosimetry of ionizing radiation is to estimate the absorbed dose by bone tissue in the human body. The bone tissues of greater radiosensitivity are the red bone marrow (RBM), that consist of the hematopoietic cells, located within the trabecular bones, and the bone surface cells (BSC), called osteogenic cells. The report 70 of the ICRP lists five spongiosa regions with their respective volume percent of trabecular bone: ribs (also contemplating the clavicles and sternum), spine, long bones, pelvis and skull (also contemplating mandible). The Grupo de Pesquisa em Dosimetria Numerica (GDN/CNPq) has been built exposure computational models (ECMs) based on voxel phantoms and EGSnrc Monte Carlo code. To estimate the energy deposited in the RBM and in the BSC of a phantom, the GDN/CNPq has used a method based on micro-CT images of the five trabecular regions mentioned above. These images were provided by other research institutes and were obtained from scan of bone samples of adult. Here is the greatest difficulty in reproducing this method: besides the need for bone images of real people with micrometer resolution, the distribution of bone marrow in the human body, according to ICRP 70, varies with age. This article presents some proposals of the GDN/CNPQ for replacing in the ECMs the micro-CT images by images synthesized by the computer, based on Monte Carlo sampling. (author)

A study of trabecular bone strength and morphometric analysis of bone microstructure from digital radiographic image

International Nuclear Information System (INIS)

Han, Seung Yun; Lee, Sun Bok; Oh, Sung Ook; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul; Park, Tae Won; Kim, Jong Dae

2003-01-01

To evaluate the relationship between morphometric analysis of microstructure from digital radiographic image and trabecular bone strength. One hundred eleven bone specimens with 5 mm thickness were obtained from the mandibles of 5 pigs. Digital images of specimens were taken using a direct digital intraoral radiographic system. After selection of ROI(100 x 100 pixel) within the trabecular bone, mean gray level and standard deviation were obtained. Fractal dimension and the variants of morphometric analysis (trabecular area, periphery, length of skeletonized trabeculae, number of terminal point, number of branch point) were obtained from ROI. Punch sheer strength analysis was performed using Instron (model 4465, Instron Corp., USA). The loading force (loading speed 1mm/min) was applied to ROI of bone specimen by a 2 mm diameter punch. Stress-deformation curve was obtained from the punch sheer strength analysis and maximum stress, yield stress, Young's modulus were measured. Maximum stress had a negative linear correlation with mean gray level and fractal dimension significantly (p<0.05). Yield stress had a negative linear correlation with mean gray level, periphery, fractal dimension and the length of skeletonized trabeculae significantly (p<0.05). Young's modulus had a negative linear correlation with mean gray level and fractal dimension significantly (p<0.05). The strength of cancellous bone exhibited a significantly linear relationship between mean gray level, fractal dimension and morphometric analysis. The methods described above can be easily used to evaluate bone quality clinically.

Bone dosimetry using synthetic images to represent trabecular bones of five regions of the human body

International Nuclear Information System (INIS)

Lima Filho, Jose de M.; Vieira, Jose W.; Lima, Vanildo J. de M.; Lima, Lindeval F.; Lima, Fernando R.A.; Vasconcelos, Wagner E. de

2011-01-01

One of the greatest challenges in numerical dosimetry of ionizing radiation is to estimate the absorbed dose by bone tissue in the human body. The bone tissues of greater radiosensitivity are the red bone marrow (RBM), that consist of the hematopoietic cells, located within the trabecular bones, and the bone surface cells (BSC), called osteogenic cells. The report 70 of the ICRP lists five spongiosa regions with their respective volume percent of trabecular bone: ribs (also contemplating the clavicles and sternum), spine, long bones, pelvis and skull (also contemplating mandible). The Grupo de Pesquisa em Dosimetria Numerica (GDN/CNPq) has been built exposure computational models (ECMs) based on voxel phantoms and EGSnrc Monte Carlo code. To estimate the energy deposited in the RBM and in the BSC of a phantom, the GDN/CNPq has used a method based on micro-CT images of the five trabecular regions mentioned above. These images were provided by other research institutes and were obtained from scan of bone samples of adult. Here is the greatest difficulty in reproducing this method: besides the need for bone images of real people with micrometer resolution, the distribution of bone marrow in the human body, according to ICRP 70, varies with age. This article presents some proposals of the GDN/CNPQ for replacing in the ECMs the micro-CT images by images synthesized by the computer, based on Monte Carlo sampling. (author)

Use of MR-based trabecular bone microstructure analysis at the distal radius for osteoporosis diagnostics: a study in post-menopausal women with breast cancer and treated with aromatase inhibitor.

Science.gov (United States)

Baum, Thomas; Karampinos, Dimitrios C; Seifert-Klauss, Vanadin; Pencheva, Tsvetelina D; Jungmann, Pia M; Rummeny, Ernst J; Müller, Dirk; Bauer, Jan S

2016-01-01

Treatment with aromatase inhibitor (AI) is recommended for post-menopausal women with hormone-receptor positive breast cancer. However, AI therapy is known to induce bone loss leading to osteoporosis with an increased risk for fragility fractures. The purpose of this study was to investigate whether changes of magnetic resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarker can already be detected in subjects with AI intake but still without evidence for osteoporosis according to dual energy X-ray absorptiometry (DXA)-based bone mineral density (BMD) measurements as current clinical gold standard. Twenty-one postmenopausal women (62±6 years of age) with hormone-receptor positive breast cancer, ongoing treatment with aromatase inhibitor for 23±15 months, and no evidence for osteoporosis (current DXA T-score greater than -2.5) were recruited for this study. Eight young, healthy women (24±2 years of age) were included as controls. All subjects underwent 3 Tesla magnetic resonance imaging (MRI) of the distal radius to assess the trabecular bone microstructure. Trabecular bone microstructure parameters were not significantly (p>0.05) different between subjects with AI intake and controls, including apparent bone fraction (0.42±0.03 vs. 0.42±0.05), trabecular number (1.95±0.10 mm(-1) vs 1.89±0.15 mm(-1)), trabecular separation (0.30±0.03 mm vs 0.31±0.06 mm), trabecular thickness (0.21±0.01 mm vs 0.22±0.02 mm), and fractal dimension (1.70±0.02 vs. 1.70±0.03). These findings suggest that the initial deterioration of trabecular bone microstructure as measured by MRI and BMD loss as measured by DXA occur not sequentially but rather simultaneously. Thus, the use of MR-based trabecular bone microstructure assessment is limited as early diagnostic biomarker in this clinical setting.

Lower trabecular volumetric BMD at metaphyseal regions of weight-bearing bones is associated with prior fracture in young girls.

Science.gov (United States)

Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

2011-02-01

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1-1.9) and 1.3 (1.0-1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. Copyright © 2011 American Society for Bone and Mineral Research.

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score.

Science.gov (United States)

Vinolas, Helene; Grouthier, Virginie; Mehsen-Cetre, Nadia; Boisson, Amandine; Winzenrieth, Renaud; Schaeverbeke, Thierry; Mesguich, Charles; Bordenave, Laurence; Tabarin, Antoine

2018-05-21

Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. University Hospital. Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P < .03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P < .04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P = .07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P < .01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P < .02). Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice. © 2018 John Wiley & Sons Ltd.

Estimating the mechanical competence parameter of the trabecular bone: a neural network approach

Directory of Open Access Journals (Sweden)

Érica Regina Filletti

Full Text Available Abstract Introduction The mechanical competence parameter (MCP of the trabecular bone is a parameter that merges the volume fraction, connectivity, tortuosity and Young modulus of elasticity, to provide a single measure of the trabecular bone structural quality. Methods As the MCP is estimated for 3D images and the Young modulus simulations are quite consuming, in this paper, an alternative approach to estimate the MCP based on artificial neural network (ANN is discussed considering as the training set a group of 23 in vitro vertebrae and 12 distal radius samples obtained by microcomputed tomography (μCT, and 83 in vivo distal radius magnetic resonance image samples (MRI. Results It is shown that the ANN was able to predict with very high accuracy the MCP for 29 new samples, being 6 vertebrae and 3 distal radius bones by μCT and 20 distal radius bone by MRI. Conclusion There is a strong correlation (R2 = 0.97 between both techniques and, despite the small number of testing samples, the Bland-Altman analysis shows that ANN is within the limits of agreement to estimate the MCP.

Bonding strength of glass-ceramic trabecular-like coatings to ceramic substrates for prosthetic applications.

Science.gov (United States)

Chen, Qiang; Baino, Francesco; Pugno, Nicola M; Vitale-Brovarone, Chiara

2013-04-01

A new approach based on the concepts of quantized fracture mechanics (QFM) is presented and discussed in this paper to estimate the bonding strength of trabecular-like coatings, i.e. glass-ceramic scaffolds mimicking the architecture of cancellous bone, to ceramic substrates. The innovative application of glass-derived scaffolds as trabecular-like coatings is proposed in order to enhance the osteointegration of prosthetic ceramic devices. The scaffolds, prepared by polymeric sponge replication, are joined to alumina substrates by a dense glass-ceramic coating (interlayer) and the so-obtained 3-layer constructs are investigated from micro-structural, morphological and mechanical viewpoints. In particular, the fracture strengths of three different crack propagation modes, i.e. glass-derived scaffold fracture, interface delamination or mixed fracture, are predicted in agreement with those of experimental mechanical tests. The approach proposed in this work could have interesting applications towards an ever more rational design of bone tissue engineering biomaterials and coatings, in view of the optimization of their mechanical properties for making them actually suitable for clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Of mice, birds, and men: the mouse ultrasonic song system has some features similar to humans and song-learning birds.

Directory of Open Access Journals (Sweden)

Gustavo Arriaga

Full Text Available Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other's pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning.

Trabecular bone strains around a dental implant and associated micromotions--a micro-CT-based three-dimensional finite element study.

Science.gov (United States)

Limbert, Georges; van Lierde, Carl; Muraru, O Luiza; Walboomers, X Frank; Frank, Milan; Hansson, Stig; Middleton, John; Jaecques, Siegfried

2010-05-07

The first objective of this computational study was to assess the strain magnitude and distribution within the three-dimensional (3D) trabecular bone structure around an osseointegrated dental implant loaded axially. The second objective was to investigate the relative micromotions between the implant and the surrounding bone. The work hypothesis adopted was that these virtual measurements would be a useful indicator of bone adaptation (resorption, homeostasis, formation). In order to reach these objectives, a microCT-based finite element model of an oral implant implanted into a Berkshire pig mandible was developed along with a robust software methodology. The finite element mesh of the 3D trabecular bone architecture was generated from the segmentation of microCT scans. The implant was meshed independently from its CAD file obtained from the manufacturer. The meshes of the implant and the bone sample were registered together in an integrated software environment. A series of non-linear contact finite element (FE) analyses considering an axial load applied to the top of the implant in combination with three sets of mechanical properties for the trabecular bone tissue was devised. Complex strain distribution patterns are reported and discussed. It was found that considering the Young's modulus of the trabecular bone tissue to be 5, 10 and 15GPa resulted in maximum peri-implant bone microstrains of about 3000, 2100 and 1400. These results indicate that, for the three sets of mechanical properties considered, the magnitude of maximum strain lies within an homeostatic range known to be sufficient to maintain/form bone. The corresponding micro-motions of the implant with respect to the bone microstructure were shown to be sufficiently low to prevent fibrous tissue formation and to favour long-term osseointegration. Copyright 2010 Elsevier Ltd. All rights reserved.

Laser Trabeculoplasty Induces Changes in the Trabecular Meshwork Glycoproteome: A pilot study

OpenAIRE

Amelinckx, Adriana; Castello, Maria; Arrieta-Quintero, Esdras; Lee, Tinthu; Salas, Nelson; Hernandez, Eleut; Lee, Richard K.; Bhattacharya, Sanjoy K.; Parel, Jean-Marie A

2009-01-01

Laser trabeculoplasty (LT) is a commonly used modality of treatment for glaucoma. The mechanism by which LT lowers the intraocular pressure (IOP) is unknown. Using cat eyes, selective laser trabeculoplasty (SLT) with a Q-switched frequency doubled Nd:YAG laser was used to treat the trabecular meshwork (TM). Laser treated TM was then subjected to proteomic analysis for detection of molecular changes and histological analysis for the detection of structural and protein expression patterns. In a...

Trabecular bone mineral density measured by quantitative CT of the lumbar spine in children and adolescents: reference values and peak bone mass

International Nuclear Information System (INIS)

Berthold, L.D.; Alzen, G.; Haras, G.; Mann, M.

2006-01-01

Purpose: The aim of this study was to assess bone density values in the trabecular substance of the lumbar vertebral column in children and young adults in Germany from infancy to the age of peak bone mass. Materials and Methods: We performed quantiative computed tomography (QCT) on the first lumbar vertebra in 28 children and adolescents without diseases that may influence bone metabolism (15 boys, 13 girls, mean ages 11 and 8 years, respectively). We also measured 17 healthy young adults (9 men, 8 women, mean ages 20 and 21 years). We used a Somatom Balance Scanner (Siemens, Erlangen) and the Siemens Osteo software. Scan parameters: Slice thickness 1 cm, 80 kV, 81 or 114 mAs. We measured the trabecular bone density and the area and height of the vertebra and calculated the volume and content of calcium hydroxyapatite (Ca-HA) in the trabecular substance of the first lumbar vertebra. Results: Prepubertal boys had a mean bone density of 148.5 (median [med] 150.1, standard deviation [SD] 15.4) mg/Ca-HA per ml bone, and prepubertal girls had a mean density of 149.5 (med 150.8, SD 23.5) mg/ml. We did not observe a difference between prepubertal boys and girls. After puberty there was a significant difference (p<0.001) between males and females: Mean density (male) 158.0, med 162.5, SD 24.0 mg/ml, mean density (female) 191.2, med 191.3, SD 17.7 mg/ml. The Ca-HA content in the trabecular bone of the first lumbar vertebra was 1.1 (med 1.1, SD 0.5) g for prepubertal boys and 1.1 (0.9, 0.4) g for prepubertal girls. For post-pubertal males, the mean Ca-HA content was 3.5 g, med 3.5 SD 0.5 g, and for post-pubertal females, the mean content was 2.8, med 2.7, SD 0.4 g. Conclusion: The normal trabecular bone mineral density is 150 mg/ml with a standard deviation of 20 mg/ml independent of age or gender until the beginning of puberty. Peak bone mass (bone mineral content) in the trabecular substance of the lumbar vertebral column is higher in males than in females, and peak bone

Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.

Science.gov (United States)

Yamauchi, Makoto; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Matsumoto, Yoshitaka; Yamashita, Ken; Kayama, Musashi; Sato, Noriyuki; Yotsuyanagi, Takatoshi

2016-05-13

Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and TNF-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-α production model using spleen cells revealed that TNF-α production was significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in kl/kl mouse may have a role to increase TNF-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

International Nuclear Information System (INIS)

Herlin, Maria; Finnilä, Mikko A.J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M.; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

2013-01-01

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr −/− ) and wild-type (Ahr +/+ ) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr +/+ mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr −/− mice displayed a slightly modified bone phenotype as compared with untreated Ahr +/+ mice, while TCDD exposure caused only a few changes in bones of Ahr −/− mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr +/+ mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

Energy Technology Data Exchange (ETDEWEB)

Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

2013-11-15

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation

Assessment of trabecular bone changes around endosseous implants using image analysis techniques: A preliminary study

International Nuclear Information System (INIS)

Zuki, Mervet El; Omami, Galal; Horner, Keith

2014-01-01

The objective of this study was to assess the trabecular bone changes that occurred around functional endosseous dental implants by means of radiographic image analysis techniques. Immediate preoperative and postoperative periapical radiographs of de-identified implant patients at the University Dental Hospital of Manchester were retrieved, screened for specific inclusion criteria, digitized, and quantified for structural elements of the trabecular bone around the endosseous implants, by using image analysis techniques. Data were analyzed using SPSS version 11.5. P values of less than 0.05 were considered statistically significant. A total of 12 implants from 11 patients were selected for the study, and 26 regions of interest were obtained. There was a significant increase in the bone area in terms of the mean distance between nodes (p=0.006) and a significant decrease in the marrow area in terms of the bone area (p=0.006) and the length of marrow spaces (p=0.032). It appeared that the bone around the implant underwent remodeling that resulted in a net increase in bone after implant placement.

Assessment of trabecular bone changes around endosseous implants using image analysis techniques: A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Zuki, Mervet El [Dept. of Oral Medicine and Radiology, Benghazi University College of Dentistry, Benghazi (Libya); Omami, Galal [Oral Diagnosis and Polyclinics, Faculty of Dentistry, The University of Hong Kong (Hong Kong); Horner, Keith [Dept. of Oral Radiology, University Dental Hospital of Manchester, Manchester (United Kingdom)

2014-06-15

The objective of this study was to assess the trabecular bone changes that occurred around functional endosseous dental implants by means of radiographic image analysis techniques. Immediate preoperative and postoperative periapical radiographs of de-identified implant patients at the University Dental Hospital of Manchester were retrieved, screened for specific inclusion criteria, digitized, and quantified for structural elements of the trabecular bone around the endosseous implants, by using image analysis techniques. Data were analyzed using SPSS version 11.5. P values of less than 0.05 were considered statistically significant. A total of 12 implants from 11 patients were selected for the study, and 26 regions of interest were obtained. There was a significant increase in the bone area in terms of the mean distance between nodes (p=0.006) and a significant decrease in the marrow area in terms of the bone area (p=0.006) and the length of marrow spaces (p=0.032). It appeared that the bone around the implant underwent remodeling that resulted in a net increase in bone after implant placement.

CBFA1 and topoisomerase I mRNA levels decline during cellular aging of human trabecular osteoblasts

DEFF Research Database (Denmark)

Christiansen, Mette; Kveiborg, M.; Kassem, M.

2000-01-01

In order to understand the reasons for age-related impairment of the function of bone forming osteoblasts, we have examined the steady-state mRNA levels of the transcription factor CBFA1 and topoisomerase I during cellular aging of normal human trabecular osteoblasts, by the use of semiquantitati...

Voxel effects within digital images of trabecular bone and their consequences on chord-length distribution measurements

International Nuclear Information System (INIS)

Rajon, D.A.; Shah, A.P.; Watchman, C.J.; Bolch, W.E.; Jokisch, D.W.; Patton, P.W.

2002-01-01

Chord-length distributions through the trabecular regions of the skeleton have been investigated since the early 1960s. These distributions have become important features for bone marrow dosimetry; as such, current models rely on the accuracy of their measurements. Recent techniques utilize nuclear magnetic resonance (NMR) microscopy to acquire 3D images of trabecular bone that are then used to measure 3D chord-length distributions by Monte Carlo methods. Previous studies have shown that two voxel effects largely affect the acquisition of these distributions within digital images. One is particularly pertinent as it dramatically changes the shape of the distribution and reduces its mean. An attempt was made to reduce this undesirable effect and good results were obtained for a single-sphere model using minimum acceptable chord (MAC) methods (Jokisch et al 2001 Med. Phys. 28 1493-504). The goal of the present work is to extend the study of these methods to more general models in order to better quantify their consequences. First, a mathematical model of a trabecular bone sample was used to test the usefulness of the MAC methods. The results showed that these methods were not efficient for this simulated bone model. These methods were further tested on a single voxelized sphere over a large range of voxel sizes. The results showed that the MAC methods are voxel-size dependent and overestimate the mean chord length for typical resolutions used with NMR microscopy. The study further suggests that bone and marrow chord-length distributions currently utilized in skeletal dosimetry models are most likely affected by voxel effects that yield values of mean chord length lower than their true values. (author)

Trabecular bone microstructure is impaired in the proximal femur of human immunodeficiency virus-infected men with normal bone mineral density.

Science.gov (United States)

Kazakia, Galateia J; Carballido-Gamio, Julio; Lai, Andrew; Nardo, Lorenzo; Facchetti, Luca; Pasco, Courtney; Zhang, Chiyuan A; Han, Misung; Parrott, Amanda Hutton; Tien, Phyllis; Krug, Roland

2018-02-01

There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis. Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA. Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV

Neocellularization and neovascularization of nanosized bioactive glass-coated decellularized trabecular bone scaffolds

KAUST Repository

Gerhardt, Lutz Christian

2012-09-11

In this study, the in vivo recellularization and neovascularization of nanosized bioactive glass (n-BG)-coated decellu-larized trabecular bone scaffolds were studied in a rat model and quantified using stereological analyses. Based on the highest amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm 2), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating density of 0.263 mg/cm2, human fibroblasts produced 4.3 times more VEGF than on uncoated controls. After 8 weeks of implantation in Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated with newly formed tissue (47-48%) and blood vessels (3-4%). No significant differences were found in cellularization and vascularization between uncoated bone scaffolds and n-BG-coated scaffolds. This finding indicates that the decellularized bone itself may exhibit growth-promoting properties induced by the highly interconnected pore microarchitecture and/or proteins left behind on decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG-coated bone scaffolds, a bioactive coating is considered to be beneficial to impart osteoinductive and osteoconductive properties to decellularized bone. n-BG-coated bone grafts have thus high clinical potential for the regeneration of complex tissue defects given their ability for recellularization and neovascularization. © 2012 Wiley Periodicals, Inc.

Texture analysis of trabecular bone using conventional radiographs: medical imaging and osteoporosis

International Nuclear Information System (INIS)

Karunanithi, R.; Panicker, T.M.R.; Paul Korath, M.; Jagadeesan, K.; Ganesan, S.

2008-01-01

Osteoporosis is characterized by reduced bone mass, microstructural deterioration with advancing age, and an increase in fracture risk. The accurate clinical assessment of bone strength and fracture risk is important for management of bone loss diseases such as osteoporosis risk. From a clinical point of view, microarchitecture is an interesting aspect to study and define patterns of bone alterations with aging and pathology. Microarchitecture seems to be a determinant of bone fragility independent of bone density. Moreover, bone microarchitecture seems to be important to understand the mechanisms of bone fragility independent of bone density. Moreover bone microarchitecture seems to be important to understand the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. In the case of osteoporosis the bone texture of the trabecular network as it appears on the plain radiographs can be quantified by applying image processing tools. Among the factors conditioning bone strength and osteoporotic fractures, bone mineral density is the most important and the best studied. Though, other factors also play a role: macroarchitecture of bones, cortical thickness, quality of bone crystal and of collagen network and trabecular microarchitecture. The microarchitecture plays a major role, and is an aspect of the definition of osteoporosis. Therefore, it would be very helpful if these alterations could be measured in addition to bone mineral density with noninvasive techniques, such as radiographs, and to assess the status of the bone by texture analysis

Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats

Directory of Open Access Journals (Sweden)

Pingping Han

2016-06-01

Full Text Available Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of 25Mg, 28Si, 39K, 47Ti, 56Fe, 59Co, 77Se, 88Sr, 137Ba, and 208Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of 28Si, 77Se, 208Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla.

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

Science.gov (United States)

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

Science.gov (United States)

Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

2016-05-01

Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.

Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice.

Science.gov (United States)

Neis, Vivian B; Bettio, Luis E B; Moretti, Morgana; Rosa, Priscila B; Ribeiro, Camille M; Freitas, Andiara E; Gonçalves, Filipe M; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone Response to Dietary Co-Enrichment with Powdered Whole Grape and Probiotics

Directory of Open Access Journals (Sweden)

Cynthia Blanton

2018-01-01

Full Text Available Nutrition is a primary modifiable determinant of chronic noncommunicable disease, including osteoporosis. An etiology of osteoporosis is the stimulation of bone-resorbing osteoclasts by reactive oxygen species (ROS. Dietary polyphenols and probiotics demonstrate protective effects on bone that are associated with reduced ROS formation and suppressed osteoclast activity. This study tested the effect of dietary enrichment with powdered whole grape and probiotics (composed of equal parts Bifidobacterium bifidum, B. breve, Lactobacillus casei, L. plantarum, and L. bulgaricus on bone microarchitecture in a mouse model of age-related osteoporosis. Groups (n = 7 each of 10-month-old male mice were fed one of six diets for 6 months: 10% grape powder with sugar corrected to 20%; 20% grape powder; 1% probiotic with sugar corrected to 20%; 10% grape powder + 1% probiotic with sugar corrected to 20%; 20% grape powder + 1% probiotic; 20% sugar control. Femur, tibia and 4th lumbar vertebrae from 10-month-old mice served as comparator baseline samples. Bone microarchitecture was measured by micro-computed tomography and compared across diet groups using analysis of variance. Aging exerted a significant effect on tibia metaphysis trabecular bone, with baseline 10-month-old mice having significantly higher bone volume/total volume (BV/TV and trabecular number measurements and lower trabecular spacing measurements than all 16-month-old groups (p < 0.001. Neither grape nor probiotic enrichment significantly improved bone microarchitecture during aging compared to control diet. The combination of 20% grape + 1% probiotic exerted detrimental effects on tibia metaphysis BV/TV compared to 10% grape + 1% probiotic, and trabecular number and trabecular spacing compared to 10% grape + 1% probiotic, 1% probiotic and control groups (p < 0.05. Femur metaphysis trabecular bone displayed less pronounced aging effects than tibia bone, but also showed detrimental effects of the

Adipose tissue depot volume relationships with spinal trabecular bone mineral density in African Americans with diabetes.

Directory of Open Access Journals (Sweden)

Gary C Chan

Full Text Available Changes in select adipose tissue volumes may differentially impact bone mineral density. This study was performed to assess cross-sectional and longitudinal relationships between computed tomography-determined visceral (VAT, subcutaneous (SAT, inter-muscular (IMAT, and pericardial adipose tissue (PAT volumes with respective changes in thoracic vertebral and lumbar vertebral volumetric trabecular bone mineral density (vBMD in African Americans with type 2 diabetes. Generalized linear models were fitted to test relationships between baseline and change in adipose volumes with change in vBMD in 300 African American-Diabetes Heart Study participants; adjustment was performed for age, sex, diabetes duration, study interval, smoking, hypertension, BMI, kidney function, and medications. Participants were 50% female with mean ± SD age 55.1±9.0 years, diabetes duration 10.2±7.2 years, and BMI 34.7±7.7 kg/m2. Over 5.3 ± 1.4 years, mean vBMD decreased in thoracic/lumbar spine, while mean adipose tissue volumes increased in SAT, IMAT, and PAT, but not VAT depots. In fully-adjusted models, changes in lumbar and thoracic vBMD were positively associated with change in SAT (β[SE] 0.045[0.011], p<0.0001; 0.40[0.013], p = 0.002, respectively. Change in thoracic vBMD was positively associated with change in IMAT (p = 0.029 and VAT (p = 0.016; and change in lumbar vBMD positively associated with baseline IMAT (p<0.0001. In contrast, vBMD was not associated with change in PAT. After adjusting for BMI, baseline and change in volumes of select adipose depots were associated with increases in thoracic and lumbar trabecular vBMD in African Americans. Effects of adiposity on trabecular bone appear to be site-specific and related to factors beyond mechanical load.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

Science.gov (United States)

Carvalho, Catarina; Magalhães, Juliana; Pereira, Luciano; Simões-Silva, Liliana; Castro-Ferreira, Inês; Frazão, João Miguel

2016-01-01

Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 μm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.

Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

Science.gov (United States)

Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

2013-12-01

The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system. © 2013 British Society for Immunology.

Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

Science.gov (United States)

Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

2015-12-01

Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

Radiographic evaluation of 19 patients with Paprosky 3A and 3B submitted to acetabular review with trabecular metal wedge

Directory of Open Access Journals (Sweden)

Carlos Eduardo Benvindo Rosal da Fonseca Neto

Full Text Available ABSTRACT Objective: This study is aimed at evaluating the fixation of trabecular metal wedges in patients who underwent revision of total hip arthroplasty with large acetabular bone defects. Methods: The radiographs of 19 patients (21 hips, who underwent revision of total hip arthroplasty using trabecular metal wedges from September 2010 to December 2014 were evaluated. This study included only cases of Paprosky 3A and 3B. Preoperative and postoperative images were analyzed. Non-fixation of the implant was defined by the presence of angular variation of the component higher 10 degrees or displacement greater than 6 mm. Patients with follow-up times of less than 24 months or who did not attend the last two appointments were excluded from the study. Results: The mean follow-up time was 39.4 months (25-61. Fixation was achieved in all cases despite its complexity. There was only one case of dislocation that was treated with open reduction. One case developed infection, and was surgically approached on two occasions, with extensive debridement and intravenous antibiotics following protocol, with good evolution. Conclusion: The implanted trabecular metal wedges showed excellent results in the short- and medium-term and may represent another option in the reconstruction of large acetabular defects, sometimes replacing bone reconstruction that uses bone tissue banks or autologous graft.

Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.

Directory of Open Access Journals (Sweden)

David F Razidlo

2010-07-01

Full Text Available Histone deacetylase (Hdac3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.

Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice.

Science.gov (United States)

Uchida, Raina; Chiba, Hiroshige; Ishimi, Yoshiko; Uehara, Mariko; Suzuki, Kazuharu; Kim, Hyounju; Matsumoto, Akiyo

2011-07-01

Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however, the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better effects on cytokines related with bone resorption.

High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice

DEFF Research Database (Denmark)

Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas

2018-01-01

that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison...... to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory...... demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin...

Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone

Energy Technology Data Exchange (ETDEWEB)

Lind, P. Monica, E-mail: Monica.Lind@medsci.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Ullerakersvaegen 40, 751 85 Uppsala (Sweden); Oberg, Denise [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Larsson, Sune [Department of Orthopaedics, Uppsala University, Uppsala (Sweden); Kyle, Carol E. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Orberg, Jan [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Rhind, Stewart M. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)

2010-05-01

Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25 tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8 months until they were 4-6 years of age and they were slaughtered at 110 d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, - 4%; p < 0.05), lower trabecular bone mineral content (BMC, mg/mm; - 18%; p < 0.05), trabecular bone mineral density (BMD, mg/cm{sup 3}, - 8.0%; p < 0.05) and trabecular CSA, mm{sup 2}, - 11.1%; p < 0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (- 6.7%, p < 0.05) and marrow cavity area (- 13.8%, p < 0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+ 3.0%, p < 0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

Human trabecular meshwork cells express BMP antagonist mRNAs and proteins.

Science.gov (United States)

Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F

2016-06-01

Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Trabecular bone strains around a dental implant and associated micromotions--a micro-CT-based three-dimensional finite element study.

NARCIS (Netherlands)

Limbert, G.; Lierde, C. van; Muraru, O.L.; Walboomers, X.F.; Frank, M.; Hansson, S.; Middleton, J.; Jaecques, S.

2010-01-01

The first objective of this computational study was to assess the strain magnitude and distribution within the three-dimensional (3D) trabecular bone structure around an osseointegrated dental implant loaded axially. The second objective was to investigate the relative micromotions between the

Protection of trabecular bone in ovariectomized rats by turmeric (Curcuma longa L.) is dependent on extract composition.

Science.gov (United States)

Wright, Laura E; Frye, Jennifer B; Timmermann, Barbara N; Funk, Janet L

2010-09-08

Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing bioactive phenolic curcuminoids were evaluated for bone-protective effects in a hypogonadal rat model of postmenopausal osteoporosis. Three-month female Sprague-Dawley rats were ovariectomized (OVX) and treated with a chemically complex turmeric fraction (41% curcuminoids by weight) or a curcuminoid-enriched turmeric fraction (94% curcuminoids by weight), both dosed at 60 mg/kg 3x per week, or vehicle alone. Effects of two months of treatment on OVX-induced bone loss were followed prospectively by serial assessment of bone mineral density (BMD) of the distal femur using dual-energy X-ray absorptiometry (DXA), while treatment effects on trabecular bone microarchitecture were assessed at two months by microcomputerized tomography (microCT). Chemically complex turmeric did not prevent bone loss, however, the curcuminoid-enriched turmeric prevented up to 50% of OVX-induced loss of trabecular bone and also preserved the number and connectedness of the strut-like trabeculae. These results suggest that turmeric may have bone-protective effects but that extract composition is a critical factor.

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

Directory of Open Access Journals (Sweden)

Timonen Jussi

2011-01-01

Full Text Available Abstract Background Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT together with peripheral quantitative computed tomography (pQCT to examine the microstructure of the distal femoral metaphysis in mice. Methods Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C, control + running (CR, high-fat diet (HF, and high-fat diet + running (HFR. After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and μCT measurements. Results The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR, with increased epididymal fat pad mass and impaired insulin sensitivity. These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia. Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure. Conclusions The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

Directory of Open Access Journals (Sweden)

Yalong Dang

2017-08-01

Full Text Available Objective The trabecular meshwork (TM is the primary substrate of outflow resistance in glaucomatous eyes. Repopulating diseased TM with fresh, functional TM cells might be a viable therapeutic approach. Decellularized TM scaffolds have previously been produced by ablating cells with suicide gene therapy or saponin, which risks incomplete cell removal or dissolution of the extracellular matrix, respectively. We hypothesized that improved trabecular meshwork cell ablation would result from freeze-thaw cycles compared to chemical treatment. Materials and Methods We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion within two hours of sacrifice. Intraocular pressure (IOP was recorded continuously by a pressure transducer system. After 72 h of IOP stabilization, eight eyes were assigned to freeze-thaw (F ablation (−80 °C × 2, to 0.02% saponin (S treatment, or the control group (C, respectively. The TM was transduced with an eGFP expressing feline immunodeficiency viral (FIV vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture media for 180 h. TM histology was assessed by hematoxylin and eosin staining. TM viability was evaluated by a calcein AM/propidium iodide (PI assay. The TM extracellular matrix was stained with Picro Sirius Red. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with five degrees of freedom. Results F and S experienced a similar IOP reduction of 30% from baseline (P = 0.64. IOP reduction of about 30% occurred in F within 24 h and in S within 48 h. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis and Picro Sirius staining confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed

The Relationship between Trabecular Bone Structure Modeling Methods and the Elastic Modulus as Calculated by FEM

Directory of Open Access Journals (Sweden)

Tomasz Topoliński

2012-01-01

Full Text Available Trabecular bone cores were collected from the femoral head at the time of surgery (hip arthroplasty. Investigated were 42 specimens, from patients with osteoporosis and coxarthrosis. The cores were scanned used computer microtomography (microCT system at an isotropic spatial resolution of 36 microns. Image stacks were converted to finite element models via a bone voxel-to-element algorithm. The apparent modulus was calculated based on the assumptions that for the elastic properties, E=10 MPa and ν=0.3. The compressive deformation as calculated by finite elements (FE analysis was 0.8%. The models were coarsened to effectively change the resolution or voxel size (from 72 microns to 288 microns or from 72 microns to 1080 microns. The aim of our study is to determine how an increase in the distance between scans changes the elastic properties as calculated by FE models. We tried to find a border value voxel size at which the module values were possible to calculate. As the voxel size increased, the mean voxel volume increased and the FEA-derived apparent modulus decreased. The slope of voxel size versus modulus relationship correlated with several architectural indices of trabecular bone.

Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

Directory of Open Access Journals (Sweden)

Sara H Windahl

Full Text Available Androgens are important regulators of bone mass but the relative importance of testosterone (T versus dihydrotestosterone (DHT for the activation of the androgen receptor (AR in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2, encoded by separate genes (Srd5a1 and Srd5a2. 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05 and cortical bone mineral content (-15%, p<0.05 but unchanged serum androgen levels compared with wild type (WT mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05 in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05. Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques.

Science.gov (United States)

Birmingham, E; Grogan, J A; Niebur, G L; McNamara, L M; McHugh, P E

2013-04-01

Bone marrow found within the porous structure of trabecular bone provides a specialized environment for numerous cell types, including mesenchymal stem cells (MSCs). Studies have sought to characterize the mechanical environment imposed on MSCs, however, a particular challenge is that marrow displays the characteristics of a fluid, while surrounded by bone that is subject to deformation, and previous experimental and computational studies have been unable to fully capture the resulting complex mechanical environment. The objective of this study was to develop a fluid structure interaction (FSI) model of trabecular bone and marrow to predict the mechanical environment of MSCs in vivo and to examine how this environment changes during osteoporosis. An idealized repeating unit was used to compare FSI techniques to a computational fluid dynamics only approach. These techniques were used to determine the effect of lower bone mass and different marrow viscosities, representative of osteoporosis, on the shear stress generated within bone marrow. Results report that shear stresses generated within bone marrow under physiological loading conditions are within the range known to stimulate a mechanobiological response in MSCs in vitro. Additionally, lower bone mass leads to an increase in the shear stress generated within the marrow, while a decrease in bone marrow viscosity reduces this generated shear stress.

Effects of Herbal-Acupuncture with Rosae Laevigatae Fructus Extract at KI10(Umgok on Osteoporosis in Ovariectomized Mice

Directory of Open Access Journals (Sweden)

Kim Dong-soo

2009-12-01

Full Text Available Objective & Methods : The purpose of this study was to observe the effects of herbal-acupuncture with Rosae Laevigatae Fructus extact(RLF-HA at KI10(Umgok on osteoporosis in ovariectomized(OVX ddy mice. We carried out several experimental items to analyze the changes in body weight, uterine weight, uterus index, tibial length, the ash bone weight, tibial BMD, serum ALP, serum osteocalcin, serum Ca, and the levels of Ca, P, Ca/P ratio in tibia, and we performed histological and histomorphological analysis as well. Results : 1. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok and saline injection at KI10(Umgok significantly inhibited the reduction of tibial calcium level in ovariectomized mice. 2. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the increase of tibial osteoclast cells in ovariectomized mice. 3. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the reduction of tibial trabecular bone thickness(TBT in ovariectomized mice. 4. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the overgrowth of tibial growth plate length(GPL in ovariectomized mice. Conclusion : These results suggested that herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok has a therapeutic effect on osteoporosis, and to be put to practical use in the future osteoporosis clinic.

Prospective case series on trabecular-iris angle status after an acute episode of phacomorphic angle closure

Directory of Open Access Journals (Sweden)

Jacky Lee

2013-02-01

Full Text Available AIM:To investigate the trabecular-iris angle with ultrasound biomicroscopy (UBM post cataract extraction after an acute attack of phacomorphic angle closure.METHODS: This prospective study involved 10 cases of phacomorphic angle closure that underwent cataract extraction and intraocular lens insertion after intraocular pressure (IOP lowering. Apart from visual acuity and IOP, the trabecular-iris angle was measured by gonioscopy and UBM at 3 months post attack.RESULTS: In 10 consecutive cases of acute phacomorphic angle closure from December 2009 to December 2010, gonioscopic findings showed peripheral anterior synechiae (PAS ≤ 90° in 30% of phacomorphic patients and a mean Shaffer grading of (3.1±1.0. UBM showed a mean angle of (37.1°±4.5° in the phacomorphic eye with the temporal quadrant being the most opened and (37.1°±8.0° in the contralateral uninvolved eye. The mean time from consultation to cataract extraction was (1.4±0.7 days and the mean total duration of phacomorphic angle closure was (3.6±2.8 days but there was no correlation to the degree of angle closure on UBM (Spearman correlation P=0.7. The presenting mean IOP was (50.5±7.4 mmHg and the mean IOP at 3 months was (10.5±3.4 mmHg but there were no correlations with the degree of angle closure (Spearman correlations P=0.9.CONCLUSION:An open trabecular-iris angle and normal IOP can be achieved after an acute attack of phacomorphic angle closure if cataract extraction is performed within 1 day - 2 days after IOP control. Gonioscopic findings were in agreement with UBM, which provided a more specific and object angle measurement. The superior angle is relatively more narrowed compared to the other quadrants. All contralateral eyes in this series had open angles.

A distinctive patchy osteomalacia characterises Phospho1-deficient mice.

Science.gov (United States)

Boyde, Alan; Staines, Katherine A; Javaheri, Behzad; Millan, Jose Luis; Pitsillides, Andrew A; Farquharson, Colin

2017-08-01

The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO) mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscale structure of bone are not yet fully elucidated. Tibias and femurs obtained from wild-type and Phospho1 null (KO) mice (25-32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections. Block surfaces were studied using 20 kV backscattered-electron (BSE) imaging, and again after iodine staining to reveal non-mineralised matrix and cellular components. For 3D characterisation, we used X-ray micro-tomography. Bones opened with carbide milling tools to expose endosteal surfaces were macerated using an alkaline bacterial pronase enzyme detergent, 5% hydrogen peroxide and 7% sodium hypochlorite solutions to produce 3D surfaces for study with 3D BSE scanning electron microscopy (SEM). Extensive regions of both compact cortical and trabecular bone matrix in Phospho1 KO mice contained no significant mineral and/or showed arrested mineralisation fronts, characterised by a failure in the fusion of the calcospherite-like, separately mineralising, individual micro-volumes within bone. Osteoclastic resorption of the uncalcified matrix in Phospho1 KO mice was attenuated compared with surrounding normally mineralised bone. The extent and position of this aberrant biomineralisation varied considerably between animals, contralateral limbs and anatomical sites. The most frequent manifestation lay, however, in the nearly complete failure of mineralisation in the bone surrounding the numerous transverse blood vessel canals in the cortices. In conclusion, SEM disclosed defective mineralising fronts and extensive patchy osteomalacia, which has previously not been recognised. These data further confirm the role of this phosphatase

Radiography of the mandible prior to endosseous implant treatment. Localization of the mandibular canal and assessment of trabecular bone

Energy Technology Data Exchange (ETDEWEB)

Lindh, C.

1996-03-01

Mandibular autopsy specimens were examined with different radiographic techniques in order to evaluate the visibility of the mandibular canal and the measurement accuracy of distances related to the mandibular canal. Hypocycloidal, spiral and computed tomography (CT) were superior to periapical and panoramic radiography in visualizing the mandibular canal. The tomographic techniques were more accurate when measurements of distances related to the mandibular canal were performed. No difference in measurement accuracy was found between the tomographic techniques. Concerning visibility of the mandibular canal, interobserver agreement was lowest for periapical radiography and highest for CT. Intraobserver agreement was moderate or good for all techniques. A high interobserver variation was found for measurability of distances related to the mandibular canal. The trabecular bone tissue in mandibular autopsy specimens was studied concerning different characteristics. A classification system to be used prior to implant treatment, based on the trabecular pattern in periapical radiographs, was proposed. 74 refs.

Radiography of the mandible prior to endosseous implant treatment. Localization of the mandibular canal and assessment of trabecular bone

International Nuclear Information System (INIS)

Lindh, C.

1996-03-01

Mandibular autopsy specimens were examined with different radiographic techniques in order to evaluate the visibility of the mandibular canal and the measurement accuracy of distances related to the mandibular canal. Hypocycloidal, spiral and computed tomography (CT) were superior to periapical and panoramic radiography in visualizing the mandibular canal. The tomographic techniques were more accurate when measurements of distances related to the mandibular canal were performed. No difference in measurement accuracy was found between the tomographic techniques. Concerning visibility of the mandibular canal, interobserver agreement was lowest for periapical radiography and highest for CT. Intraobserver agreement was moderate or good for all techniques. A high interobserver variation was found for measurability of distances related to the mandibular canal. The trabecular bone tissue in mandibular autopsy specimens was studied concerning different characteristics. A classification system to be used prior to implant treatment, based on the trabecular pattern in periapical radiographs, was proposed. 74 refs

Trabecular Meshwork Height in Primary Open-Angle Glaucoma Versus Primary Angle-Closure Glaucoma.

Science.gov (United States)

Masis, Marisse; Chen, Rebecca; Porco, Travis; Lin, Shan C

2017-11-01

To determine if trabecular meshwork (TM) height differs between primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) eyes. Prospective, cross-sectional clinical study. Adult patients were consecutively recruited from glaucoma clinics at the University of California, San Francisco, from January 2012 to July 2015. Images were obtained from spectral-domain optical coherence tomography (Cirrus OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA). Univariate and multivariate linear mixed models comparing TM height and glaucoma type were performed to assess the relationship between TM height and glaucoma subtype. Mixed-effects regression was used to adjust for the use of both eyes in some subjects. The study included 260 eyes from 161 subjects, composed of 61 men and 100 women. Mean age was 70 years (SD 11.77). There were 199 eyes (123 patients) in the POAG group and 61 eyes (38 patients) in the PACG group. Mean TM heights in the POAG and PACG groups were 812 ± 13 μm and 732 ± 27 μm, respectively, and the difference was significant in univariate analysis (P = .004) and in multivariate analysis (β = -88.7 [24.05-153.5]; P = .008). In this clinic-based population, trabecular meshwork height is shorter in PACG patients compared to POAG patients. This finding may provide insight into the pathophysiology of angle closure and provide assistance in future diagnosis, prevention, and management of the angle-closure spectrum of disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture.

Science.gov (United States)

Redondo, L; Puigoriol, E; Rodríguez, J R; Peris, P; Kanterewicz, E

2018-04-01

The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice.

Science.gov (United States)

Seto, Jong; Busse, Björn; Gupta, Himadri S; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W C; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi

2012-01-01

The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix--a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

Directory of Open Access Journals (Sweden)

Aw MS

2012-09-01

Full Text Available Moom Sinn Aw,1 Kamarul A Khalid,2,3 Karan Gulati,1 Gerald J Atkins,2 Peter Pivonka,4 David M Findlay,2 Dusan Losic11School of Chemical Engineering, 2Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, SA, Australia; 3Department of Orthopaedics, Traumatology and Rehabilitation, Faculty of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 4Engineering Computational Biology Group, School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, AustraliaPurpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti wires generated with titania nanotube (TNT arrays as drug-releasing implants for local drug deliveryMethods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm and horizontal (0–10 mm distances from the implant surface were obtained at a range of release times from 1 hour to 5 days.Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex

Influence of the pore fluid on the phase velocity in bovine trabecular bone In Vitro: Prediction of the biot model

Science.gov (United States)

Lee, Kang Il

2013-01-01

The present study aims to investigate the influence of the pore fluid on the phase velocity in bovine trabecular bone in vitro. The frequency-dependent phase velocity was measured in 20 marrow-filled and water-filled bovine femoral trabecular bone samples. The mean phase velocities at frequencies between 0.6 and 1.2 MHz exhibited significant negative dispersions for both the marrow-filled and the water-filled samples. The magnitudes of the dispersions showed no significant differences between the marrow-filled and the water-filled samples. In contrast, replacement of marrow by water led to a mean increase in the phase velocity of 27 m/s at frequencies from 0.6 to 1.2 MHz. The theoretical phase velocities of the fast wave predicted by using the Biot model for elastic wave propagation in fluid-saturated porous media showed good agreements with the measurements.

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

Science.gov (United States)

Ben Kahla, Rabeb; Barkaoui, Abdelwahed; Merzouki, Tarek

2018-05-04

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

Science.gov (United States)

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-06-01

The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution

Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice.

Science.gov (United States)

Fonseca, Tatiana L; Teixeira, Marilia B C G; Miranda-Rodrigues, Manuela; Rodrigues-Miranda, Manuela; Silva, Marcos V; Martins, Gisele M; Costa, Cristiane C; Arita, Danielle Y; Perez, Juliana D; Casarini, Dulce E; Brum, Patricia C; Gouveia, Cecilia H A

2014-08-15

To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T3 treatment in a supraphysiological dose for 12 wk on the bone of young adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, α(2A)-AR, and α(2C)-AR (α(2A/2C)-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DEXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by μCT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, α(2A/2C)-AR(-/-) mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α(2A/2C)-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α(2A/2C)-AR(-/-) mice. As expected, T3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young adult mice and suggests that this interaction may involve α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology. Copyright © 2014 the American Physiological Society.

Bone mineral density and trabecular bone tissue quality in obese men

Directory of Open Access Journals (Sweden)

V.V. Povoroznyuk

2017-02-01

Full Text Available Obesity and osteoporosis are the two metabolic dise­ases with increased prevalence over last decades and a strong impact on the global morbidity and mortality have gained a status of major health threats worldwide. There is evidence that the higher body mass index (BMI values are associated with greater bone mineral density (BMD resulting in a site-specific protective effect for fragility fractures. On the other hand, higher BMI values increases incidence of falls and is associated with worse fractures consolidation. However, trabecular bone score (TBS indirectly explores bone quali­ty, independently of BMD. The aim of the study was to determine the connection between the BMD and TBS parameters in Ukrainian men suffering from obesity. Methods. We examined 396 men aged 40–89 years, by the BMI all the subjects were divided into 2 groups: Group A — with obesity and BMI ≥ 30 kg/m2 (n = 129 and Group B — without obesity and BMI < 30 kg/m2 (n = 267. The BMD of total body, lumbar spine at the site L1–L4, femur and forearm were measured by DXA (Prodigy, GEHC Lunar, Madison, WI, USA. The TBS of L1–L4 was assessed by means of TBS iNsight (Med-Imaps, Pessac, France. Results. In general, obese men had a significantly higher BMD of lumbar spine, femoral neck, total body and ultradistal forearm (p < 0.001 in comparison with men without obesity. The TBS of L1–L4 was significantly lower in obese men compared to non-obese men (p < 0.001. The significant positive correlation between the fat mass and the BMD at different sites was observed. The correlation between the fat mass and TBS of L1–L4 was also significant, but negative. Conclusions. Obesity negatively affects the quality of trabecular bone, while bone mineral density was significantly higher.

Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating

NARCIS (Netherlands)

Biemond, J.E.; Hannink, G.; Verdonschot, Nicolaas Jacobus Joseph; Buma, P.

2013-01-01

The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and

[Radiographic appraisal between metal and bone interosculate backfill after total hip arthroplasty with trabecular metal cup].

Science.gov (United States)

Li, Wei; Zhou, Yi-Xin; Wu, Jian; Xu, Hui; Ji, Song-Jie

2009-02-15

To evaluate the bone refilling in the interface between the trabecular metal (TM) acetabular shell and the bone surface according to consecutive X film measuring after surgery. From July 2006 to July 2007, 35 patients (40 hips) accepted total hip replacement using trabecular metal monoblock acetabular cup system (TM). The cup was made of a ellipse shaped press fit Tantalum shell and high cross-linked PE liner (Longevity) with 28 mm inner diameter. The patients demography was: 16 male (20 hips), 19 female (20 hips), 5 bilateral hip replacements, age from 41 - 71 (mean 53), including 18 avascular necrosis hips, 16 osteoarthritis hips (including those secondary to a dysplasia hip), 4 avascular necrosis hips after femoral neck fracture, 2 Ankylosis Spondylitis. All the 40 total hip replacements used posterior approach, using hemispherical acetabular reamer and 2 mm press fit of final metal shell without screw fixation. The consecutive X film was taken at the end time of surgery and 2, 6, 12, 24 weeks, and 12 months. The clinical results was evaluate according to Harris scoring system, and the standard pelvis AP X film was measured at the interface between metal shell and the acetabular bone surface, witch was divided into five regions (A, B, C, D, E). Totally 32 patients (37 hips) were followed with average 8.7 months (7 - 12 months). The Harris before surgery was 50.5 (32 - 85), promoted to 91.0 (72 - 100), including 29 excellent, 6 good, 2 fair, and the total excellent and good rate was 94.6%. Complications include 4 patients leg length discrepancy from 1 - 2 cm, 3 patients moderate thigh pain and released after conservative therapy. No infection and dislocation was found. Twenty-one patients (23 hips) were found lucent line at the bone-metal interface from 1 - 5 mm, most common in B region and BC boundary than C, D, and CD boundary. All the patients followed was found the lucent line disappeared and refilled with bone at X film 24 weeks after surgery, however, no

Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

Directory of Open Access Journals (Sweden)

Hongbin Lu

Full Text Available This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point. The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate

One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletons.

Science.gov (United States)

Gerbaix, Maude; Gnyubkin, Vasily; Farlay, Delphine; Olivier, Cécile; Ammann, Patrick; Courbon, Guillaume; Laroche, Norbert; Genthial, Rachel; Follet, Hélène; Peyrin, Françoise; Shenkman, Boris; Gauquelin-Koch, Guillemette; Vico, Laurence

2017-06-01

The weightless environment during spaceflight induces site-specific bone loss. The 30-day Bion-M1 mission offered a unique opportunity to characterize the skeletal changes after spaceflight and an 8-day recovery period in mature male C57/BL6 mice. In the femur metaphysis, spaceflight decreased the trabecular bone volume (-64% vs. Habitat Control), dramatically increased the bone resorption (+140% vs. Habitat Control) and induced marrow adiposity invasion. At the diaphysis, cortical thinning associated with periosteal resorption was observed. In the Flight animal group, the osteocyte lacunae displayed a reduced volume and a more spherical shape (synchrotron radiation analyses), and empty lacunae were highly increased (+344% vs. Habitat Control). Tissue-level mechanical cortical properties (i.e., hardness and modulus) were locally decreased by spaceflight, whereas the mineral characteristics and collagen maturity were unaffected. In the vertebrae, spaceflight decreased the overall bone volume and altered the modulus in the periphery of the trabecular struts. Despite normalized osteoclastic activity and an increased osteoblast number, bone recovery was not observed 8 days after landing. In conclusion, spaceflight induces osteocyte death, which may trigger bone resorption and result in bone mass and microstructural deterioration. Moreover, osteocyte cell death, lacunae mineralization and fatty marrow, which are hallmarks of ageing, may impede tissue maintenance and repair.

Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

Energy Technology Data Exchange (ETDEWEB)

Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il [Department of Materials Science and Engineering, Techion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Zaretzky, Asaph [The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096 Israel (Israel); Psakhie, Sergey G. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation)

2015-10-27

The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were divided in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.

Osteoporosis Recovery by Antrodia camphorata Alcohol Extracts through Bone Regeneration in SAMP8 Mice

Directory of Open Access Journals (Sweden)

Hen-Yu Liu

2016-01-01

Full Text Available Antrodia camphorata has previously demonstrated the efficacy in treating cancer and anti-inflammation. In this study, we are the first to evaluate Antrodia camphorata alcohol extract (ACAE for osteoporosis recovery in vitro with preosteoblast cells (MC3T3-E1 and in vivo with an osteoporosis mouse model established in our previous studies, ovariectomized senescence accelerated mice (OVX-SAMP8. Our results demonstrated that ACAE treatment was slightly cytotoxic to preosteoblast at 25 μg/mL, by which the osteogenic gene expression (RUNX2, OPN, and OCN was significantly upregulated with an increased ratio of OPG to RANKL, indicating maintenance of the bone matrix through inhibition of osteoclastic pathway. Additionally, evaluation by Alizarin Red S staining showed increased mineralization in ACAE-treated preosteoblasts. For in vivo study, our results indicated that ACAE inhibits bone loss and significantly increases percentage bone volume, trabecular bone number, and bone mineral density in OVX-SAMP8 mice treated with ACAE. Collectively, in vitro and in vivo results showed that ACAE could promote osteogenesis and prevent bone loss and should be considered an evidence-based complementary and alternative medicine for osteoporosis therapy through the maintenance of bone health.

Age-related changes in trabecular and cortical bone microstructure.

Science.gov (United States)

Chen, Huayue; Zhou, Xiangrong; Fujita, Hiroshi; Onozuka, Minoru; Kubo, Kin-Ya

2013-01-01

The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT), micro-CT, and high resolution peripheral quantitative CT (HR-pQCT), imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

Crohn’s disease and Trabecular Metal implants: a report of two cases and literature review

Directory of Open Access Journals (Sweden)

C. Peron

2015-10-01

Full Text Available Aim The aim of the present study was to report two cases with Crohn’s disease in whom dental implants successfully osseointegrated and remained functionally stable up to 13 and 12 months of follow-up, respectively. Cases presentation In cases 1 (age 35 years and 2 (age 36 years, tooth 24 and 14, respectively, were atraumatically extracted and a particulated bone grafting material (buccal and palatal aspect of the defect and a Trabecular Metal implant (11.5 mm length, 4.7 mm diameter were inserted in each extraction socket. After implant placement and abutment connection with the final torque (25 Ncm, the provisional restoration was adapted in the oral cavity creating the emergence profile. The provisional crown was screw-retained and had slight occlusal contacts in the centric occlusion (intercuspation position. A periapical radiograph was taken as a control radiograph at the baseline. Postoperatively, antibiotics were prescribed as well as analgesics and an oral rinse was recommended. In both cases, the provisional restoration was removed after 2 weeks and replaced with a full ceramic restoration. Case-1 and case-2 were followed up after 13 months and 12 months respectively. In both cases postoperative healing was uneventful and radiographs taken at follow-up showed no evidence of crestal bone loss. Implants in both cases demonstrated an excellent clinical condition at follow-up. Conclusion Trabecular Metal implants can osseointegrate and remain functionally stable in patients with Crohn’s disease.

Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis.

Science.gov (United States)

Xie, Fen; Zhou, Bin; Wang, Jian; Liu, Tang; Wu, Xiyu; Fang, Rui; Kang, Yijun; Dai, Ruchun

2018-03-05

The microstructure of autologous bone grafts from men over 50 years old and postmenopausal women undergoing spinal fusion were evaluated using micro-CT. We demonstrated postmenopausal women, especially those with osteoporosis (OP) presented more serious microarchitectural deterioration of bone grafts. This study was undertaken to determine microstructural properties of cancellous bone used as autologous bone grafts from osteoporosis patients undergoing lumbar fusion by comparing microstructural indices to controls. Cancellous bone specimens from spinous processes were obtained from 41 postmenopausal women (osteoporosis women, n = 19; controls, n = 22) and 26 men over 50 years old (osteoporosis men, n = 8; controls, n = 18) during lumbar fusion surgery. The microstructural parameters were measured using micro-CT. Significant difference in bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th), and structure model index (SMI) value existed between postmenopausal women with OP and controls. Significant difference in trabecular number (Tb.N) existed between men over 50 years old with OP and controls. Postmenopausal women exhibited lower BV/TV, Tb.Th, and higher SMI value than men over 50 years old. Postmenopausal women with OP exhibited lower BV/TV, Tb.Th, and higher BS/BV than men over 50 years old with OP. Post-menopausal women and older men with OP have worse bone quality in autografts than non-osteoporotic men and women. Postmenopausal women with OP presented serious microarchitectural deterioration in older population.

Cost-effectiveness analysis of iStent trabecular microbypass stent for patients with open-angle glaucoma in Colombia

OpenAIRE

Osorio, Urpy; Ordoñez, Angelica

2018-01-01

Objective: To estimate cost-effectiveness of trabecular micro bypass stent versus laser trabeculoplasty or medications only, for patients with open-angle glaucoma in setting of Colombian System Health. Methods: This is a cost-effectiveness analysis that based its assumptions in external data sources, used to extrapolate the quality of life related to health, survival and costs. A Markov model, with stages from 0 (ocular hypertension without glaucoma) to 5 and bilateral blindness, was develope...

Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.

Science.gov (United States)

Niehoff, Anja; Lechner, Philipp; Ratiu, Oana; Reuter, Sven; Hamann, Nina; Brüggemann, Gert-Peter; Schönau, Eckhard; Bloch, Wilhelm; Beccard, Ralf

2014-04-01

Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 μg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

DEFF Research Database (Denmark)

Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

2015-01-01

Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

Development of a 3-D x-ray micro-tomography system and its application to trabecular bone/cement interface

International Nuclear Information System (INIS)

Chi, Yong Ki; Cho, Gyuseong

2004-01-01

In recent years, the interface analysis of micro-structure based objects is an important research in osteoporosis, vascular imaging since a 3-D X-ray micro-tomography system was developed. However, the micro-tomographic image shows the white-out appearance in case of imaging of similar density objects with low energy X-ray. Therefore these images must be analyzed about the interface between microstructure based objects for its application to biomechanical study. Many published studies suggested approximately assumed model of interface and predicted mechanical failure by means of Finite Element Method (FEM) but these FEM analysis has not used for modeling the real structure and interface between objects such as roughness, voids and pores of objects. We developed micro-tomography system and suggest the application of micro-tomographic image for predicting mechanical failure at the interface. The micro-tomography system consists of a 5 μm micro-focus X-ray tube, a CMOS-based image sensor and a rotating sample holder controlled by a precision motor. CMOS image sensor has 62x62 mm 2 sensing area and uses optical lenses system for increasing resolution. The sample which was manufactured by implanting cement in a pig hip bone was used and its fracture is considered to be an important cause of loosening of hip joint replacement in orthopedic implants. A Feldkamp's cone-beam reconstruction algorithm on the equispatial detector case was used for bone/cement 3D volume data and the analysis of a trabecular bone/cement interface containing white-out appearance was performed by using multiple criterion segmentation of region and volume. Finally, the segmented data can be used for fracture prediction of FEM by determining node of hexahedron meshing. In this paper, we present development of a 3-D cone beam micro-tomographic system with CMOS image sensor and its application to a complex structure of a trabecular bone and implanted cement for predicting the failure mechanism of

Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

Directory of Open Access Journals (Sweden)

Mathilde Doyard

Full Text Available Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Science.gov (United States)

Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

2014-01-01

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS

Zinc metabolism in genetically obese mice

International Nuclear Information System (INIS)

Kennedy, M.L.; Failla, M.L.

1986-01-01

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65 Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65 Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65 Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65 Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

Assessment of spinal trabecular bone by quantitative CT

International Nuclear Information System (INIS)

Adachi, Toshiki; Kozakura, Yoshihiro; Kato, Isamu; Yamamoto, Yoshio

1988-01-01

127 normal values of spinal trabecular bone mineral content (BMC) for 67 males (age range : 20 ∼ 77) and 60 females (age range : 23 ∼ 76) were studied by quantitative computed tomography (QCT). We have measured L1, L2 and L3 vertebrae, but there is no significant difference between L1, L2 and L3 BMC, so we caliculated the individual BMC from the average of the three vertebrae data. The BMC value was found to be greatly enfluenced by age. Its maximum at the age of 20 years for males and females, and decreases gradually with an increase in age with a much more reduction seen in the females. The mean value of BMC for the males was approximately 171 mg/ml K 2 HPO 4 equivalent to the 20 - 40 age range years and the females was approximately 183 mg/ml, so that by the age 70, the males were reduced by 35 % to approximately 110 mg/ml, the females were reduced by 50 % to approximately 92 mg/ml. The interrelation was analyzed by using a cubic regression study which revealed an adequate correlation (r = 0.77 in the males, r = 0.85 in the females) between BMC and age. (author)

Differential Canalograms Detect Outflow Changes from Trabecular Micro-Bypass Stents and Ab Interno Trabeculectomy.

Science.gov (United States)

Parikh, Hardik A; Loewen, Ralitsa T; Roy, Pritha; Schuman, Joel S; Lathrop, Kira L; Loewen, Nils A

2016-11-04

Recently introduced microincisional glaucoma surgeries that enhance conventional outflow offer a favorable risk profile over traditional surgeries, but can be unpredictable. Two paramount challenges are the lack of an adequate training model for angle surgeries and the absence of an intraoperative quantification of surgical success. To address both, we developed an ex vivo training system and a differential, quantitative canalography method that uses slope-adjusted fluorescence intensities of two different chromophores to avoid quenching. We assessed outflow enhancement by trabecular micro-bypass (TMB) implantation or by ab interno trabeculectomy (AIT). In this porcine model, TMB resulted in an insignificant (p > 0.05) outflow increase of 13 ± 5%, 14 ± 8%, 9 ± 3%, and 24 ± 9% in the inferonasal, superonasal, superotemporal, and inferotemporal quadrant, respectively. AIT caused a 100 ± 50% (p = 0.002), 75 ± 28% (p = 0.002), 19 ± 8%, and 40 ± 21% increase in those quadrants. The direct gonioscopy and tactile feedback provided a surgical experience that was very similar to that in human patients. Despite the more narrow and discontinuous circumferential drainage elements in the pig with potential for underperformance or partial stent obstruction, unequivocal patterns of focal outflow enhancement by TMB were seen in this training model. AIT achieved extensive access to outflow pathways beyond the surgical site itself.

Cassava is not a goitrogen in mice

International Nuclear Information System (INIS)

Hershman, J.M.; Pekary, A.E.; Sugawara, M.; Adler, M.; Turner, L.; Demetriou, J.A.; Hershman, J.D.

1985-01-01

To examine the effect of cassava on the thyroid function of mice, the authors fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [ 125 I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5'-monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5'-monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man

Axial compressive strength of human vertebrae trabecular bones classified as normal, osteopenic and osteoporotic by quantitative ultrasonometry of calcaneus

Directory of Open Access Journals (Sweden)

Reinaldo Cesar

2017-06-01

Full Text Available Abstract Introduction Biomechanical assessment of trabecular bone microarchitecture contributes to the evaluation of fractures risk associated with osteoporosis and plays a crucial role in planning preventive strategies. One of the most widely clinical technics used for osteoporosis diagnosis by health professionals is bone dual-energy X-ray absorptiometry (DEXA. However, doubts about its accuracy motivate the introduction of congruent technical analysis such as calcaneal ultrasonometry (Quantitative Ultrasonometry - QUS. Methods Correlations between Bone Quality Index (BQI, determined by calcaneal ultrasonometry of thirty (30 individuals classified as normal, osteopenic and osteoporotic, and elastic modulus (E and ultimate compressive strength (UCS from axial compression tests of ninety (90 proof bodies from human vertebrae trabecular bone, which were extracted from cadavers in the twelfth thoracic region (T12, first and fourth lumbar (L1 and L4. Results Analysis of variance (ANOVA showed significant differences for E (p = 0.001, for UCS (p = 0.0001 and BQI. Spearman’s rank correlation coefficient (rho between BQI and E (r = 0.499 and BQI and UCS (r = 0.508 were moderate. Discussion Calcaneal ultrasonometry technique allowed a moderate estimate of bone mechanical strength and fracture risk associated with osteoporosis in human vertebrae.

Using Non-linear Homogenization to Improve the Performance of Macroscopic Damage Models of Trabecular Bone.

Science.gov (United States)

Levrero-Florencio, Francesc; Pankaj, Pankaj

2018-01-01

Realistic macro-level finite element simulations of the mechanical behavior of trabecular bone, a cellular anisotropic material, require a suitable constitutive model; a model that incorporates the mechanical response of bone for complex loading scenarios and includes post-elastic phenomena, such as plasticity (permanent deformations) and damage (permanent stiffness reduction), which bone is likely to experience. Some such models have been developed by conducting homogenization-based multiscale finite element simulations on bone micro-structure. While homogenization has been fairly successful in the elastic regime and, to some extent, in modeling the macroscopic plastic response, it has remained a challenge with respect to modeling damage. This study uses a homogenization scheme to upscale the damage behavior from the tissue level (microscale) to the organ level (macroscale) and assesses the suitability of different damage constitutive laws. Ten cubic specimens were each subjected to 21 strain-controlled load cases for a small range of macroscopic post-elastic strains. Isotropic and anisotropic criteria were considered, density and fabric relationships were used in the formulation of the damage law, and a combined isotropic/anisotropic law with tension/compression asymmetry was formulated, based on the homogenized results, as a possible alternative to the currently used single scalar damage criterion. This computational study enhances the current knowledge on the macroscopic damage behavior of trabecular bone. By developing relationships of damage progression with bone's micro-architectural indices (density and fabric) the study also provides an aid for the creation of more precise macroscale continuum models, which are likely to improve clinical predictions.

Polycythemia is associated with bone loss and reduced osteoblast activity in mice.

Science.gov (United States)

Oikonomidou, P R; Casu, C; Yang, Z; Crielaard, B; Shim, J H; Rivella, S; Vogiatzi, M G

2016-04-01

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO). PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO. Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2(V617F) knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO. Compared to wt, both JAK2(V617F) and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

International Nuclear Information System (INIS)

Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

1990-01-01

Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

Assessment of spinal trabecular bone by quantitative computed tomography

International Nuclear Information System (INIS)

Soya, Toshio; Seto, Hikaru; Futatsuya, Ryusuke; Kamei, Tetsuya; Kakishita, Masao

1987-01-01

151 normal values of spinal trabecular bone mineral content (BMC) for 79 men and 72 women were studied by single energy quantitative computed tomography (QCT). The BMC value has a great relation to age. It has a maximum in the age of 20 years in men and in the age of 20 ∼ 30 years in women, and decreases gradually after these ages with a more rapid reduction in women (1.1 % per year in men and 1.6 % per year in women). In younger generation (under 50 years of age) the average value of the BMC is 180 mg/ml K 2 HPO 4 equivalent in men, 189 mg/ml in women, and in older generation, is 123 mg/ml and 112 mg/ml respectively. In the individual case, the fluctuation of inter-vertebrae (L1, L2 and L3) has large variation, therefore, to estimate one's BMC enoughly the measurement of at least three vertebrae should be done. There found no physical factor which attributes to the BMC value. It is suggested that the BMC are affected by age and sex. (author)

Age-Related Changes in Trabecular and Cortical Bone Microstructure

Directory of Open Access Journals (Sweden)

Huayue Chen

2013-01-01

Full Text Available The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT, micro-CT, and high resolution peripheral quantitative CT (HR-pQCT, imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

Automated selection of trabecular bone regions in knee radiographs

International Nuclear Information System (INIS)

Podsiadlo, P.; Wolski, M.; Stachowiak, G. W.

2008-01-01

Osteoarthritic (OA) changes in knee joints can be assessed by analyzing the structure of trabecular bone (TB) in the tibia. This analysis is performed on TB regions selected manually by a human operator on x-ray images. Manual selection is time-consuming, tedious, and expensive. Even if a radiologist expert or highly trained person is available to select regions, high inter- and intraobserver variabilities are still possible. A fully automated image segmentation method was, therefore, developed to select the bone regions for numerical analyses of changes in bone structures. The newly developed method consists of image preprocessing, delineation of cortical bone plates (active shape model), and location of regions of interest (ROI). The method was trained on an independent set of 40 x-ray images. Automatically selected regions were compared to the ''gold standard'' that contains ROIs selected manually by a radiologist expert on 132 x-ray images. All images were acquired from subjects locked in a standardized standing position using a radiography rig. The size of each ROI is 12.8x12.8 mm. The automated method results showed a good agreement with the gold standard [similarity index (SI)=0.83 (medial) and 0.81 (lateral) and the offset=[-1.78, 1.27]x[-0.65,0.26] mm (medial) and [-2.15, 1.59]x[-0.58, 0.52] mm (lateral)]. Bland and Altman plots were constructed for fractal signatures, and changes of fractal dimensions (FD) to region offsets calculated between the gold standard and automatically selected regions were calculated. The plots showed a random scatter and the 95% confidence intervals were (-0.006, 0.008) and (-0.001, 0.011). The changes of FDs to region offsets were less than 0.035. Previous studies showed that differences in FDs between non-OA and OA bone regions were greater than 0.05. ROIs were also selected by a second radiologist and then evaluated. Results indicated that the newly developed method could replace a human operator and produces bone regions

Electron absorbed fractions of energy and S-values in an adult human skeleton based on {mu}CT images of trabecular bone

Energy Technology Data Exchange (ETDEWEB)

Kramer, R; Cassola, V F; Khoury, H J; De O Lira, C A B [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Professor Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Richardson, R B [Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, ON, K0J 1J0 (Canada); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); Brown, K Robson, E-mail: rkramer@uol.com.br [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)

2011-03-21

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on {mu}CT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 {mu}m thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters {sup 14}C, {sup 59}Fe, {sup 131}I, {sup 89}Sr, {sup 32}P and {sup 90}Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 {mu}m endosteum and the previously recommended 10 {mu}m endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by {approx}20% when the beta emitters are in marrow.

Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

Directory of Open Access Journals (Sweden)

S. Kahraman

2015-01-01

Full Text Available Nonobese Diabetic (NOD mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ. STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

Immunobiology of congenitally athymic-asplenic mice

International Nuclear Information System (INIS)

Gershwin, M.E.; Ahmed, A.; Ikeda, R.M.; Shifrine, M.; Wilson, F.

1978-01-01

A study has been made of congenitally athymic-asplenic mice obtained by the mating of nude by hereditarily asplenic (Dh/+) mice. The mice survived for up to 9 months, under specific pathogen-free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice were similar to those of their nude and asplenic littermates, there were a number of major immunologic differences. The athymic-asplenic mice appeared more immunologically compromised than nude mice. There was an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. There was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired. (author)

Trabecular bone microarchitecture analysis, a way for an early detection of genetic dwarfism? Case study of a dwarf mother's offspring.

Science.gov (United States)

Colombo, Antony; Hoogland, Menno; Coqueugniot, Hélène; Dutour, Olivier; Waters-Rist, Andrea

2018-03-01

A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Because the mutation is autosomal dominant, these perinates have a 50% risk of having been affected. This study determines whether trabecular bone microarchitecture (TBMA) analysis is useful for detecting genetic dwarfism. Proximal metaphyses of humeri were μCT-scanned with a resolution of 7-12 μm. Three volumes of interest were segmented from each bone with TIVMI© software. The TBMA was quantified in BoneJ© using six parameters on which a multivariate analysis was then performed. Two of the Middenbeemster perinates show a quantitatively different TBMA organization. These results and the family's medical history suggest a diagnosis of genetic dwarfism for this two perinates. This study provides evidence to support the efficacy of μCT for diagnosing early-stage bone disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Strength through structure: visualization and local assessment of the trabecular bone structure

International Nuclear Information System (INIS)

Raeth, C; Monetti, R; Bauer, J; Sidorenko, I; Mueller, D; Matsuura, M; Lochmueller, E-M; Zysset, P; Eckstein, F

2008-01-01

The visualization and subsequent assessment of the inner human bone structures play an important role for better understanding the disease- or drug-induced changes of bone in the context of osteoporosis giving prospect for better predictions of bone strength and thus of the fracture risk of osteoporotic patients. In this work, we show how the complex trabecular bone structure can be visualized using μCT imaging techniques at an isotropic resolution of 26 μm. We quantify these structures by calculating global and local topological and morphological measures, namely Minkowski functionals (MFs) and utilizing the (an-)isotropic scaling index method (SIM) and by deriving suitable texture measures based on MF and SIM. Using a sample of 151 specimens taken from human vertebrae in vitro, we correlate the texture measures with the mechanically measured maximum compressive strength (MCS), which quantifies the strength of the bone probe, by using Pearson's correlation coefficient. The structure parameters derived from the local measures yield good correlations with the bone strength as measured in mechanical tests. We investigate whether the performance of the texture measures depends on the MCS value by selecting different subsamples according to MCS. Considering the whole sample the results for the newly defined parameters are better than those obtained for the standard global histomorphometric parameters except for bone volume/total volume (BV/TV). If a subsample consisting only of weak bones is analysed, the local structural analysis leads to similar and even better correlations with MCS as compared to BV/TV. Thus, the MF and SIM yield additional information about the stability of the bone especially in the case of weak bones, which corroborates the hypothesis that the bone structure (and not only its mineral mass) constitutes an important component of bone stability.

Transplantation of canine osteosarcoma into nude mice

International Nuclear Information System (INIS)

Shifrine, M.; Taylor, N.; Holloway, G.; Arnstein, P.R.; Chrisp, C.; Pool, R.; Whaley, C.

1975-01-01

Osteosarcomas from dogs were inoculated subcutaneously into mice. Sixty days later six mice had tumors that gradually increased in size. All tumors were undifferentiated sarcomas. Karyotypes of osteosarcomas grown in tissue culture and of tumors from mice inoculated with the culture were similar with two marker chromosomes. It was thus shown that radioinduced osteosarcomas can be cultivated in tissue culture while retaining their marker chromosomes and malignancy

Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

Science.gov (United States)

Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

2016-05-01

Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Clinical Application of Solid Model Based on Trabecular Tibia Bone CT Images Created by 3D Printer.

Science.gov (United States)

Cho, Jaemo; Park, Chan-Soo; Kim, Yeoun-Jae; Kim, Kwang Gi

2015-07-01

The aim of this work is to use a 3D solid model to predict the mechanical loads of human bone fracture risk associated with bone disease conditions according to biomechanical engineering parameters. We used special image processing tools for image segmentation and three-dimensional (3D) reconstruction to generate meshes, which are necessary for the production of a solid model with a 3D printer from computed tomography (CT) images of the human tibia's trabecular and cortical bones. We examined the defects of the mechanism for the tibia's trabecular bones. Image processing tools and segmentation techniques were used to analyze bone structures and produce a solid model with a 3D printer. These days, bio-imaging (CT and magnetic resonance imaging) devices are able to display and reconstruct 3D anatomical details, and diagnostics are becoming increasingly vital to the quality of patient treatment planning and clinical treatment. Furthermore, radiographic images are being used to study biomechanical systems with several aims, namely, to describe and simulate the mechanical behavior of certain anatomical systems, to analyze pathological bone conditions, to study tissues structure and properties, and to create a solid model using a 3D printer to support surgical planning and reduce experimental costs. These days, research using image processing tools and segmentation techniques to analyze bone structures to produce a solid model with a 3D printer is rapidly becoming very important.

Long-term Risedronate Treatment Normalizes Mineralization and Continues to Preserve Trabecular Architecture: Sequential Triple Biopsy Studies with Micro-Computed Tomography

International Nuclear Information System (INIS)

Borah, B.; Dufresne, T.; Ritman, E.; Jorgensen, S.; Liu, S.; Chmielewski, P.; Phipps, R.; Zhou, X.; Sibonga, J.; Turner, R.

2006-01-01

The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 ± 1.1%, P = 0.016) and Peak-MIN (6.2 ± 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 ± 7.3%, P = 0.016) and BMR-S (-50.2 ± 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

Science.gov (United States)

Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

2017-10-01

Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice.

Science.gov (United States)

Park, Bongkyun; Song, Hae Seong; Kwon, Jeong Eun; Cho, Se Min; Jang, Seon-A; Kim, Mi Yeon; Kang, Se Chan

2017-12-20

Extracts from Salvia miltiorrhiza Bunge have been used in traditional Asian medicine to treat coronary heart disease, chronic renal failure, atherosclerosis, myocardial infraction, angina pectoris, myocardial ischemia, dysmenorrheal, neurasthenic insomnia, liver fibrosis and cirrhosis. The aim of the study was to investigate the anti-RANK signal effect of the combination of S.miltiorrhiza Bunge (SME) and liquefied calcium (LCa) supplement with ovariectomized (OVX-SML) mice, a osteoporosis animal model. Results were compared to 17β-estradiol (E 2 ) treatment. A total of 70 female ICR strain mice (7 weeks) were randomly divided into 10 groups with 7 mice in each group as follows: (1) sham-operated control mice (sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through oral administration. (2) OVX mice received a daily oral administration of PBS (OVX). (3) OVX mice treated daily with 50 mg/kg b.w./ day of SME (4) with 100 mg/kg b.w./day of SME or (5) with 200 mg/kg b.w./day of SME via oral administration. (6) OVX mice treated daily with 50 mg/kg b.w./day of SML (7) with 100 mg/kg b.w./day of SML or (8) with 200 mg/kg b.w./day of SML via oral administration. (9) OVX mice treated daily with 10 ml/kg b.w./day of LCa (10) OVX mice received i.p. injections of 17β-estradiol (E 2 ) (0.1 mg/kg b.w./day) three times per week for 12 weeks. micro-CT analysis revealed that oral administration of SML inhibited tibial bone loss, sustained trabecular bone state, and ameliorated bone biochemical markers. In addition, SML administration compared to SEM and LCa reduced serum levels of RANKL, osteocalcin and BALP through increased serum levels of OPG and E 2 in OVX mice. SML also had more beneficial effects on protection of estrogen-dependent bone loss through blocking expression of TRAF6 and NFTAc1 and produces cathepsin K and calcitonin receptor to develop osteoclast differentiation. These data suggest that S. miltiorrhiza Bunge combined with

Similar reliability and equivalent performance of female and male mice in the open field and water‐maze place navigation task

Science.gov (United States)

Fritz, Ann‐Kristina; Amrein, Irmgard

2017-01-01

Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water‐maze and in 4,554 mice tested in the same open field arena. Confidence intervals for Cohen's d as measure of effect size were computed and tested for equivalence with 0.2 as equivalence margin. Despite the large sample size, only few behavioral parameters showed a significant sex effect on CV. Confidence intervals of effect size indicated that CV was either equivalent or showed a small sex difference at most, accounting for less than 2% of total group to group variation of CV. While female mice were potentially slightly more variable in water‐maze acquisition and in the open field, males tended to perform less reliably in the water‐maze probe trial. In addition to evaluating variability, we also directly compared mean performance of female and male mice and found them to be equivalent in both water‐maze place navigation and open field exploration. Our data confirm and extend other large scale studies in demonstrating that including female mice in experiments does not cause a relevant increase of data variability. Our results make a strong case for including mice of both sexes whenever open field or water‐maze are used in preclinical research. PMID:28654717

Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH/PTHrP receptor.

Science.gov (United States)

Maeda, Yukiko; Schipani, Ernestina; Densmore, Michael J; Lanske, Beate

2010-02-01

Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation and osteoblast differentiation during prenatal endochondral bone formation. Ihh expression in postnatal chondrocytes has a non-redundant role in maintaining a growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal chondrocytes results in fusion of the growth plate and a decrease in trabecular bone. In order to normalize this abnormal chondrocyte phenotype and to investigate whether a putative rescue of the growth plate anomalies is sufficient to correct the severe alterations in the bone, we expressed a constitutively active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2 alpha 1-Cre ER; Ihh(dld) mice by mating Col2 alpha 1-Cre ER; Ihh(fl/fl) mice with Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen, J). Col2 alpha 1-Cre ER; Ihh(f/f); J mice were then injected with tamoxifen at P0 to generate Col2 alpha 1-Cre ER; Ihh(d/d); J mice. In contrast with the previously reported growth plate phenotype of Col2 alpha 1-Cre ER; Ihh(d/d) mice that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha 1-Cre ER; Ihh(d/d); J double mutants were well organized, and exhibited a gene expression pattern similar to the one of control mice. However, expression of osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the bone collar of Col2 alpha 1-Cre ER; Ihh(d/d); J mice when compared to control mice despite the rescue of abnormal chondrocyte differentiation. Moreover, proliferation of chondrocytes was still significantly impaired in Col2 alpha 1-Cre ER; Ihh(d/d); J mice, and this eventually led to the fusion of the growth plate at P14. In summary, we have demonstrated that expression of a Jansen receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation but not impaired chondrocyte proliferation and the bone anomalies in mice lacking the Ihh gene in

Sclerostin antibody treatment improves the bone phenotype of Crtap−/− mice, a model of recessive Osteogenesis Imperfecta

Science.gov (United States)

Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

2016-01-01

Osteogenesis Imperfecta (OI) is characterized by low bone mass, poor bone quality and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1 and 6 week old Crtap−/− mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of “pediatric” and “young adult” recessive OI. Vehicle treated Crtap−/− and wildtype (WT) mice served as controls. Compared with control Crtap−/− mice, microCT analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab treated Crtap−/− mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole bone strength in Crtap−/− mice, with more robust effects in the week 6–12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6–12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen post-translational modification. PMID:26716893

Characterization of micro-invasive trabecular bypass stents by ex vivo perfusion and computational flow modeling

Directory of Open Access Journals (Sweden)

Hunter KS

2014-03-01

Full Text Available Kendall S Hunter,1 Todd Fjield,2 Hal Heitzmann,2 Robin Shandas,1 Malik Y Kahook3 1Department of Bioengineering, University of Colorado Denver, Aurora, CO, USA; 2Glaukos Corporation, Laguna Hills, CA, USA; 3University of Colorado Hospital Eye Center, Aurora, CO, USA Abstract: Micro-invasive glaucoma surgery with the Glaukos iStent® or iStent inject® (Glaukos Corporation, Laguna Hills, CA, USA is intended to create a bypass through the trabecular meshwork to Schlemm's canal to improve aqueous outflow through the natural physiologic pathway. While the iStent devices have been evaluated in ex vivo anterior segment models, they have not previously been evaluated in whole eye perfusion models nor characterized by computational fluid dynamics. Intraocular pressure (IOP reduction with the iStent was evaluated in an ex vivo whole human eye perfusion model. Numerical modeling, including computational fluid dynamics, was used to evaluate the flow through the stents over physiologically relevant boundary conditions. In the ex vivo model, a single iStent reduced IOP by 6.0 mmHg from baseline, and addition of a second iStent further lowered IOP by 2.9 mmHg, for a total IOP reduction of 8.9 mmHg. Computational modeling showed that simulated flow through the iStent or iStent inject is smooth and laminar at physiological flow rates. Each stent was computed to have a negligible flow resistance consistent with an expected significant decrease in IOP. The present perfusion results agree with prior clinical and laboratory studies to show that both iStent and iStent inject therapies are potentially titratable, providing clinicians with the opportunity to achieve lower target IOPs by implanting additional stents. Keywords: glaucoma, iStent, trabecular bypass, intraocular pressure, ab-interno, CFD

Otolith dysfunction alters exploratory movement in mice.

Science.gov (United States)

Blankenship, Philip A; Cherep, Lucia A; Donaldson, Tia N; Brockman, Sarah N; Trainer, Alexandria D; Yoder, Ryan M; Wallace, Douglas G

2017-05-15

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiphoton gonioscopy to image the trabecular meshwork of porcine eyes

Science.gov (United States)

Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

2013-03-01

The aqueous outflow system (AOS), including the trabecular meshwork (TM), the collector channels (CC) and the Schlemm's canal (SC), regulates intraocular pressure (IOP) through the drainage of the aqueous humor (AH). Abnormal IOP elevation leads to increased pressure stress to retinal ganglion cells, resulting in cell loss that can ultimately lead to complete loss of eyesight. Therefore, development of imaging tools to detect abnormal structural and functional changes of the AOS is important in early diagnosis and prevention of glaucoma. Multiphoton microscopy (MPM), including twophoton autofluorescence (TPAF) and second harmonic generation (SHG), is a label-free microscopic technique that allows molecular specific imaging of biological tissues like the TM. Since the TM and other AOS structures are located behind the highly scattering scleral tissue, transscleral imaging of the TM does not provide enough optical resolution. In this work, a gonioscopic lens is used to allow direct optical access of the TM through the cornea for MPM imaging. Compared to transscleral imaging, the acquired MPM images show improved resolution as individual collagen fiber bundles of the TM can be observed. MPM gonioscopy may have the potential to be developed as a future clinical imaging tool for glaucoma diagnostics.

Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy

Science.gov (United States)

Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

2013-03-01

The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans.

Similar reliability and equivalent performance of female and male mice in the open field and water-maze place navigation task.

Science.gov (United States)

Fritz, Ann-Kristina; Amrein, Irmgard; Wolfer, David P

2017-09-01

Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water-maze and in 4,554 mice tested in the same open field arena. Confidence intervals for Cohen's d as measure of effect size were computed and tested for equivalence with 0.2 as equivalence margin. Despite the large sample size, only few behavioral parameters showed a significant sex effect on CV. Confidence intervals of effect size indicated that CV was either equivalent or showed a small sex difference at most, accounting for less than 2% of total group to group variation of CV. While female mice were potentially slightly more variable in water-maze acquisition and in the open field, males tended to perform less reliably in the water-maze probe trial. In addition to evaluating variability, we also directly compared mean performance of female and male mice and found them to be equivalent in both water-maze place navigation and open field exploration. Our data confirm and extend other large scale studies in demonstrating that including female mice in experiments does not cause a relevant increase of data variability. Our results make a strong case for including mice of both sexes whenever open field or water-maze are used in preclinical research. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

Biglycan deficiency interferes with ovariectomy-induced bone loss

DEFF Research Database (Denmark)

Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A

2003-01-01

Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response...

Similar reliability and equivalent performance of female and male mice in the open field and water-maze place navigation task

OpenAIRE

Fritz, Ann-Kristina; Amrein, Irmgard; Wolfer, David P.

2017-01-01

Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water-maze and in 4,554 mice tested in the same open field arena. Confidence intervals for C...

Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice

Directory of Open Access Journals (Sweden)

Xiaoxue Xu

2017-01-01

Full Text Available Cistanoside A (Cis A, an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP, deoxypyridinoline (DPD and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6, an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB and phosphatidylinositol 3-kinase (PI3K/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL, downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG, PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease.

Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate

Directory of Open Access Journals (Sweden)

Barbara M. Misof

2016-12-01

Full Text Available Odanacatib (ODN is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN on bone mineralization density distribution (BMDD, based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS in 12–22 years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n = 8, odanacatib low dose (ODN-L, n = 8, odanacatib high dose (ODN-H, n = 8, and alendronate (ALN, n = 6 treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n = 8. In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p < 0.001 consistent with the significant reduction of MS/BS (p < 0.05 in ODN-H and ALN compared to VEH. Vertebral trabecular CaMean (average degree of mineralization was significantly higher in ODN-L (+6.5%, ODN-H (+6.1%, and ALN (+6.7%, all p < 0.001. Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+1.4%, p < 0.05, ODN-H (+2.2%, p < 0.05, and ALN (+3.4%, p < 0.001 versus VEH, while primary cortical bone (devoid of secondary osteons did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45 ± 12% was also not significantly different between the study groups (p = 0.232. No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are

Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells

Directory of Open Access Journals (Sweden)

Qiong Liao

2016-06-01

Full Text Available AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3 make effect on outflow facility through the trabecular meshwork (TM. METHODS: Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC cells were determined, still were the collagen, type IV, alpha 1 (COL4A1 and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS: The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION: Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1. Reduced NOS3 restrains the TM cell cycle progression at the G2/M-phase transition and induced cell apoptosis.

Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice.

Directory of Open Access Journals (Sweden)

Pu-Hyeon Cha

Full Text Available The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV, one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.

Machine learning based analytics of micro-MRI trabecular bone microarchitecture and texture in type 1 Gaucher disease.

Science.gov (United States)

Sharma, Gulshan B; Robertson, Douglas D; Laney, Dawn A; Gambello, Michael J; Terk, Michael

2016-06-14

Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Anisotropic 3D Minkowski Functionals for Trabecular Bone Characterization and Biomechanical Strength Prediction in Proximal Femur Specimens

Science.gov (United States)

Nagarajan, Mahesh B.; De, Titas; Lochmüller, Eva-Maria; Eckstein, Felix; Wismüller, Axel

2017-01-01

The ability of Anisotropic Minkowski Functionals (AMFs) to capture local anisotropy while evaluating topological properties of the underlying gray-level structures has been previously demonstrated. We evaluate the ability of this approach to characterize local structure properties of trabecular bone micro-architecture in ex vivo proximal femur specimens, as visualized on multi-detector CT, for purposes of biomechanical bone strength prediction. To this end, volumetric AMFs were computed locally for each voxel of volumes of interest (VOI) extracted from the femoral head of 146 specimens. The local anisotropy captured by such AMFs was quantified using a fractional anisotropy measure; the magnitude and direction of anisotropy at every pixel was stored in histograms that served as a feature vectors that characterized the VOIs. A linear multi-regression analysis algorithm was used to predict the failure load (FL) from the feature sets; the predicted FL was compared to the true FL determined through biomechanical testing. The prediction performance was measured by the root mean square error (RMSE) for each feature set. The best prediction performance was obtained from the fractional anisotropy histogram of AMF Euler Characteristic (RMSE = 1.01 ± 0.13), which was significantly better than MDCT-derived mean BMD (RMSE = 1.12 ± 0.16, p<0.05). We conclude that such anisotropic Minkowski Functionals can capture valuable information regarding regional trabecular bone quality and contribute to improved bone strength prediction, which is important for improving the clinical assessment of osteoporotic fracture risk. PMID:29170581

Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

Directory of Open Access Journals (Sweden)

Kang-Yung Peng

2011-01-01

Full Text Available The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX mice. Microcomputed tomography (μCT analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD, trabecular bone volume/total volume (BV/TV, and trabecular bone number (Tb.N in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.

Assessment of bone mineral density by DXA and the trabecular microarchitecture of the calcaneum by texture analysis in pre- and postmenopausal women in the evaluation of osteoporosis

Directory of Open Access Journals (Sweden)

Karunanithi R

2007-01-01

Full Text Available The in vivo evaluation of trabecular bone structure could be useful in the diagnosis of osteoporosis for the characterization of therapeutic response and understanding the role of parameters other than bone mineral density (BMD in defining skeletal status. This study was made to evaluate changes taking place in the trabecular architecture of bone with age and menopausal status in women. The findings are compared with the femoral neck bone as well as the trochantar bone mineral density determined by dual energy X-ray absorptiometry (DXA, which is a standard reference test for evaluation of osteoporosis. Seventy females were recruited for the study, 25 pre-menopausal (mean age ± SD: 39.4 ± 3.8 and 45 postmenopausal (mean age ± SD: 57.9 ± 7.9 women. The right femoral neck bone mineral density was measured for them by dual energy X-ray absorptiometry (DXA. For the same individuals, lateral view radiographs of the right calcaneum were taken as well. The radiographs were digitized and the region of interest (ROI of 256 x 256 pixels was selected, the run-length matrix was computed for calculating seven parameters [Table 1] and the two-dimensional fast Fourier transform of the image was calculated. Using the FFT, the power spectral density (PSD was derived and the root mean square (RMS value was determined. Our results confirm that age has a significant influence on the texture of the trabecular bone and bone mineral density.

Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage.

Science.gov (United States)

Hilton, Matthew J; Tu, Xiaolin; Long, Fanxin

2007-08-01

Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development by signaling to both chondrocytes and perichondrial cells. Previous efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smoothened (Smo, encoding a transmembrane protein indispensable for Ihh signaling) has been only partially successful, due to the inability to discriminate between chondrocytes and perichondrial cells. Here we report a transgenic line (Col2-Cre) expressing under the control of the Colalpha1(II) promoter an inert form of Cre that is activatable by exogenous tamoxifen (TM); TM administration at proper times during embryogenesis induced Cre activity in chondrocytes but not in the perichondrium. By using this mouse line, we deleted Smo within subsets of chondrocytes without affecting the perichondrium and found that Smo removal led to localized disruption of the expression of parathyroid hormone-related protein (PTHrP) and the morphology of chondrocytes. Unexpectedly, TM invariably induced Cre activity in a subset of cells associated with the trabecular bone surface of long bones. These cells, when genetically marked and cultured in vitro, were capable of producing bone nodules. Expression of the Col2-Cre transgene in these cells likely reflected the endogenous Colalpha1(II) promoter activity as similar cells were found to express the IIA isoform of Colalpha1(II) mRNA endogenously. In summary, the present study has not only provided evidence that Ihh signaling directly controls PTHrP expression and chondrocyte morphology in the growth region cartilage, but has also uncovered a distinct cell type associated with the trabecular bone that appears to possess osteogenic potential.

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

Science.gov (United States)

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

Preliminary result on trabecular bone score (TBS in lumbar vertebrae with experimentally altered microarchitecture

Directory of Open Access Journals (Sweden)

M. Di Stefano

2013-01-01

Full Text Available The aim of this preliminary research is to investigate the reliability of a new qualitative parameter, called Trabecular Bone Score (TBS, recently proposed for evaluating the microarchitectural arrangement of cancellous bone in scans carried out by dual energy X-ray absorptiometry (DXA. Vertebral bodies of 15 fresh samples of lumbar spines of adult pig were analysed either in basal conditions and with altered microarchitecture of the cancellous bone obtained by progressive drilling. The examined bony areas do not show changes in bone mineral density (BMD, whereas TBS values decrease with the increasing alteration of the vertebral microtrabecular structure. Our preliminary data seem to confirm the reliability of TBS as a qualitative parameter useful for evaluating the microarchitectural strength in bony areas quantitatively analysed by DXA.

Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts.

Directory of Open Access Journals (Sweden)

Jason W Ashley

Full Text Available CD68 is a member of the lysosome associated membrane protein (LAMP family that is restricted in its expression to cells of the monocyte/macrophage lineage. This lineage restriction includes osteoclasts, and, while previous studies of CD68 in macrophages and dendritic cells have proposed roles in lipid metabolism, phagocytosis, and antigen presentation, the expression and function of CD68 in osteoclasts have not been explored. In this study, we investigated the expression and localization of CD68 in macrophages and osteoclasts in response to the monocyte/macrophage-colony stimulating factor (M-CSF and the receptor activator of NF-κB ligand (RANKL. We found that M-CSF stimulates CD68 expression and RANKL alters the apparent molecular weight of CD68 as measured by Western immunoblotting. In addition, we explored the significance of CD68 expression in osteoclasts by generating mice that lack expression of CD68. These mice have increased trabecular bone, and in vitro assessment of CD68(-/- osteoclasts revealed that, in the absence of CD68, osteoclasts demonstrate an accumulation of intracellular vesicle-like structures, and do not efficiently resorb bone. These findings demonstrate a role for CD68 in the function of osteoclasts, and future studies will determine the mechanistic nature of the defects seen in CD68(-/- osteoclasts.

Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke.

Science.gov (United States)

Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

2014-12-01

Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources.

New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study.

Science.gov (United States)

Lee, Jin Whan; Wen, Hai Bo; Gubbi, Prabhu; Romanos, Georgios E

2018-02-01

This study evaluated new bone formation activities and trabecular bone microarchitecture within the highly porous region of Trabecular Metal™ Dental Implants (TM) and between the threads of Tapered Screw-Vent® Dental Implants (TSV) in fresh canine extraction sockets. Eight partially edentulated dogs received four implants (4.1 mmD × 13 mmL) bilaterally in mandibular fresh extraction sockets (32 TM, 32 TSV implants), and allowed to heal for 2, 4, 8, and 12 weeks. Calcein was administered to label mineralizing bone at 11 and 4 days before euthanasia for dogs undergoing all four healing periods. Biopsies taken at each time interval were examined histologically. Histomorphometric assay was conducted for 64 unstained and 64 stained slides at the region of interest (ROI) (6 mm long × 0.35 mm deep) in the midsections of the implants. Topographical and chemical analyses were also performed. Histomorphometry revealed significantly more new bone in the TM than in the TSV implants at each healing time (p = .0014, .0084, .0218, and .0251). Calcein-labeled data showed more newly mineralized bone in the TM group than in the TSV group at 2, 8, and 12 weeks (p = .045, .028, .002, respectively) but not at 4 weeks (p = .081). Histologically TM implants exhibited more bone growth and dominant new immature woven bone at an earlier time point than TSV implants. The parameters representing trabecular bone microarchitecture corroborated faster new bone formation in the TM implants when compared to the TSV implants. TM exhibited an irregular faceted topography compared to a relatively uniform microtextured surface for TSV. Chemical analysis showed peaks associated with each implant's composition material, and TSV also showed peaks reflecting the elements of the calcium phosphate blasting media. Results suggest that the healing pathway associated with the highly porous midsection of TM dental implant could enable faster and stronger secondary implant stability than

Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

Science.gov (United States)

Kato, Kota; Ohbuchi, Masato; Hamamura, Satoko; Ohshita, Hiroki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Sato, Koya; Nakada, Naoyuki; Kawamura, Akio; Usui, Takashi; Kamimura, Hidetaka; Tateno, Chise

2015-08-01

We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Identification of a constitutive law for trabecular bone samples under remodeling in the framework of irreversible thermodynamics

Science.gov (United States)

Louna, Zineeddine; Goda, Ibrahim; Ganghoffer, Jean-François

2018-01-01

We construct in the present paper constitutive models for bone remodeling based on micromechanical analyses at the scale of a representative unit cell (RUC) including a porous trabecular microstructure. The time evolution of the microstructure is simulated as a surface remodeling process by relating the surface growth remodeling velocity to a surface driving force incorporating a (surface) Eshelby tensor. Adopting the framework of irreversible thermodynamics, a 2D constitutive model based on the setting up of the free energy density and a dissipation potential is identified from FE simulations performed over a unit cell representative of the trabecular architecture obtained from real bone microstructures. The static and evolutive effective properties of bone at the scale of the RUC are obtained by combining a methodology for the evaluation of the average kinematic and static variables over a prototype unit cell and numerical simulations with controlled imposed first gradient rates. The formulated effective growth constitutive law at the scale of the homogenized set of trabeculae within the RUC is of viscoplastic type and relates the average growth strain rate to the homogenized stress tensor. The postulated model includes a power law function of an effective stress chosen to depend on the first and second stress invariants. The model coefficients are calibrated from a set of virtual testing performed over the RUC subjected to a sequence of loadings. Numerical simulations show that overall bone growth does not show any growth kinematic hardening. The obtained results quantify the strength and importance of different types of external loads (uniaxial tension, simple shear, and biaxial loading) on the overall remodeling process and the development of elastic deformations within the RUC.

Reconstitution of the gastrointestinal microflora of lactobacillus-free mice.

OpenAIRE

Tannock, G W; Crichton, C; Welling, G W; Koopman, J P; Midtvedt, T

1988-01-01

A colony of mice that do not harbor lactobacilli in their digestive tracts but whose intestinal microflora is otherwise functionally similar to that of conventional animals was derived. Methods used to reconstitute the intestinal microflora of the mice included inoculation of the animals with cultures of specific microbes, noncultivable microbes attached to epithelial cells, and cecal contents from conventional mice treated with chloramphenicol. Twenty-six microflora-associated characteristic...

Sarcopenia in older mice is characterized by a decreased anabolic response to a protein meal.

Science.gov (United States)

van Dijk, Miriam; Nagel, Jolanda; Dijk, Francina J; Salles, Jerôme; Verlaan, Sjors; Walrand, Stephane; van Norren, Klaske; Luiking, Yvette

Ageing is associated with sarcopenia, a progressive decline of skeletal muscle mass, muscle quality and muscle function. Reduced sensitivity of older muscles to respond to anabolic stimuli, i.e. anabolic resistance, is part of the underlying mechanisms. Although, muscle parameters have been studied in mice of various ages/strains; the aim was to study if mice display similar deteriorating processes as human ageing. Therefore, 10,16,21 and 25 months-old C57BL6/6J male mice were studied to measure parameters of sarcopenia and factors contributing to its pathophysiology, with the aim of characterizing sarcopenia in old mice. Muscle mass of the hind limb was lower in 25 as compared to 10 month-old mice. A significant decrease in physical daily activity, muscle grip strength and ex vivo muscle maximal force production was observed in 25 compared to 10 month-old mice. The muscle anabolic response to a single protein meal showed increased muscle protein synthesis in young, but not in old mice, indicative to anabolic resistance. However, by increasing the protein content in meals, anabolic resistance could be overcome, similar as in human elderly. Additionally, aged mice showed higher fasted insulin and hepatic malondialdehyde (MDA) levels (=marker oxidative stress). This study shows clear characteristics of sarcopenia that coincide with anabolic resistance, insulin resistance and oxidative stress in 25 month-old C57/BL6 male mice, similar to human ageing. Furthermore, similar decline in muscle mass, strength and function was observed in this aged-mice-model. These observations offer potential for the future to explore in old mice the effects of interventions targeting sarcopenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro and in silico characterization of open-cell structures of trabecular bone.

Science.gov (United States)

Ramos-Infante, S J; Pérez, M A

2017-11-01

This work aimed to perform a detailed in vitro and in silico characterization of open-cell structures, which resemble trabecular bone, to elucidate osteoporosis failure mechanisms. Experimental and image-based computational methods were used to estimate Young's modulus and porosities of different open-cell structures (Sawbones; Malmö, Sweden). Three different open-cell structures with different porosities were characterized. Additionally, some open-cell structures were scanned using a microcomputed tomography system (μCT) to non-destructively predict specimen Young's modulus of the structures by developing voxel-based and tetrahedral finite element (FE) models. A 3D reconstruction and FE analyses were used. The experimental and computational results with different element types (linear and quadratic tetrahedrons and voxel-based meshes) were compared with Sawbones data (Sawbones; Malmö, Sweden) revealing important differences in Young's modulus and porosities. The specimens with high and low volume fractions were best represented by linear and quadratic tetrahedrons, respectively. These results could be used to develop new osteoporosis-prevention strategies.

Laser Trabeculoplasty Induces Changes in the Trabecular Meshwork Glycoproteome: A pilot study

Science.gov (United States)

Amelinckx, Adriana; Castello, Maria; Arrieta-Quintero, Esdras; Lee, Tinthu; Salas, Nelson; Hernandez, Eleut; Lee, Richard K.; Bhattacharya, Sanjoy K.; Parel, Jean-Marie A

2009-01-01

Laser trabeculoplasty (LT) is a commonly used modality of treatment for glaucoma. The mechanism by which LT lowers the intraocular pressure (IOP) is unknown. Using cat eyes, selective laser trabeculoplasty (SLT) with a Q-switched frequency doubled Nd:YAG laser was used to treat the trabecular meshwork (TM). Laser treated TM was then subjected to proteomic analysis for detection of molecular changes and histological analysis for the detection of structural and protein expression patterns. In addition, the protein glycosylation patterns of laser treated and non-treated TM was assessed and differentially glycosylated proteins were proteomically identified. SLT laser treatment to the TM resulted in elevated glycosylation levels compared to non-lasered TM. TM laser treatment also resulted in protein expression levels changes of several proteins. Elevated levels of biglycan, keratocan and prolargin were detected in laser treated TM compared to non-lasered controls. Further investigation is anticipated to provide insight into how glycosylation changes affect TM proteins and TM regulation of aqueous outflow in response to laser trabeculoplasty. PMID:19432485

Beryllium-induced immune response in C3H mice

Energy Technology Data Exchange (ETDEWEB)

Benson, J.M.; Bice, D.E.; Nikula, K.J. [and others

1995-12-01

Studies conducted at ITRI over the past several years have investigated whether Beagle dogs, monkeys, and mice are suitable models for human chronic beryllium-induced lung disease (CBD). Recent studies have focused on the histopathological and immunopathological changes occurring in A/J and C3H/HeJ mice acutely exposed by inhalation to Be metal. Lung lesions in both strains of mice included focal lymphocyte aggregates comprised primarily of B lymphocytes and lesser amounts of T-helper lymphocytes and microgranulomas consisting chiefly of macrophages and T-helper lymphocytes. The distribution of proliferating cells within the microgranulomas was similar to the distribution of T-helper cells. These results strongly suggested that A/J and C3H/HeJ mice responded to inhaled Be metal in a fashion similar to humans in terms of pulmonary lesions and the apparent in situ proliferation of T-helper cells. Results of these studies confirm lymphocyte involvement in the pulmonary response to inhaled Be metal.

Trabecular bone mineral density measured by quantitative CT of the lumbar spine in children and adolescents: reference values and peak bone mass; Trabekulaere Knochendichte der Lendenwirbelsaeule bei Kindern und Jugendlichen in der quantitativen CT: Referenzwerte und Peak Bone Mass

Energy Technology Data Exchange (ETDEWEB)

Berthold, L.D.; Alzen, G. [Kinderradiologie, Zentrum fuer Radiologie, Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen (Germany); Haras, G. [Siemens AG, Medical Solutions, Forchheim (Germany); Mann, M. [AG Medizinische Statistik, Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen (Germany)

2006-12-15

Purpose: The aim of this study was to assess bone density values in the trabecular substance of the lumbar vertebral column in children and young adults in Germany from infancy to the age of peak bone mass. Materials and Methods: We performed quantiative computed tomography (QCT) on the first lumbar vertebra in 28 children and adolescents without diseases that may influence bone metabolism (15 boys, 13 girls, mean ages 11 and 8 years, respectively). We also measured 17 healthy young adults (9 men, 8 women, mean ages 20 and 21 years). We used a Somatom Balance Scanner (Siemens, Erlangen) and the Siemens Osteo software. Scan parameters: Slice thickness 1 cm, 80 kV, 81 or 114 mAs. We measured the trabecular bone density and the area and height of the vertebra and calculated the volume and content of calcium hydroxyapatite (Ca-HA) in the trabecular substance of the first lumbar vertebra. Results: Prepubertal boys had a mean bone density of 148.5 (median [med] 150.1, standard deviation [SD] 15.4) mg/Ca-HA per ml bone, and prepubertal girls had a mean density of 149.5 (med 150.8, SD 23.5) mg/ml. We did not observe a difference between prepubertal boys and girls. After puberty there was a significant difference (p<0.001) between males and females: Mean density (male) 158.0, med 162.5, SD 24.0 mg/ml, mean density (female) 191.2, med 191.3, SD 17.7 mg/ml. The Ca-HA content in the trabecular bone of the first lumbar vertebra was 1.1 (med 1.1, SD 0.5) g for prepubertal boys and 1.1 (0.9, 0.4) g for prepubertal girls. For post-pubertal males, the mean Ca-HA content was 3.5 g, med 3.5 SD 0.5 g, and for post-pubertal females, the mean content was 2.8, med 2.7, SD 0.4 g. Conclusion: The normal trabecular bone mineral density is 150 mg/ml with a standard deviation of 20 mg/ml independent of age or gender until the beginning of puberty. Peak bone mass (bone mineral content) in the trabecular substance of the lumbar vertebral column is higher in males than in females, and peak bone

Osteoblast-targeted overexpression of TAZ increases bone mass in vivo.

Directory of Open Access Journals (Sweden)

Jae-Yeon Yang

Full Text Available Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ. Whole body bone mineral density (BMD of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7% and trabecular number (26.6% with a reciprocal decrease in trabecular spacing (14.2% in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8% and the serum P1NP level was also significantly increased (53% in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β-mediated signaling. In addition, TAZ enhanced TGF

Gene expression changes in the colon epithelium are similar to those of intact colon during late inflammation in interleukin-10 gene deficient mice.

Directory of Open Access Journals (Sweden)

Anna E Russ

Full Text Available In addition to their role in absorption and secretion, epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are important for the maintenance of homeostasis. Microarray analysis of intact colon samples is widely used to gain an overview of the cellular pathways and processes that are active in the colon during inflammation. Laser microdissection of colon epithelial cells allows a more targeted analysis of molecular pathways in the mucosa, preceding and during inflammation, with potentially increased sensitivity to changes in specific cell populations. The aim of this study was to investigate the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of inflammatory bowel diseases. Microarray analysis of intact colon samples and microdissected colon epithelial cell samples from interleukin-10 gene deficient and control mice at 6 and 12 weeks of age was undertaken. Results of gene set enrichment analysis showed that more immune-related pathways were identified between interleukin-10 gene deficient and control mice at 6 weeks of age in epithelial cells than intact colon. This suggests that targeting epithelial cells could increase sensitivity for detecting immune changes that occur early in the inflammatory process. However, in the later stages of inflammation, microarray analyses of intact colon and epithelium both provide a similar overview of gene expression changes in the colon mucosa at the pathway level.

Use of dual energy X-ray absorptiometry, the trabecular bone score and quantitative computed tomography in the evaluation of chronic kidney disease-mineral and bone disorders.

Science.gov (United States)

Pocock, Nicholas

2017-03-01

In subjects with chronic kidney disease (CKD) who suffer a minimal trauma fracture, the problem is to differentiate between osteoporosis and the various forms of renal bone disease associated with CKD-mineral and bone disorder. This problem is exacerbated by the fact that renal osteodystrophy may coexist with osteoporosis. The World Health Organization's bone mineral density (BMD) criteria for osteopenia ( -2.5 < T-score < -1.0) and osteoporosis (a T-score ≤ -2.5) may be used in patients with CKD stages 1-3. In CKD stages 4-5, BMD by dual-energy X-ray absorptiometry (DXA) is less predictive and may underestimate fracture risk. The development of absolute fracture risk (AFR) algorithms, such as FRAX® and the Garvan absolute fracture risk calculator, to predict risk of fracture over a given time (usually 10 years) aims to incorporate non-BMD risk factors into the clinical assessment. FRAX® has been shown to be useful to assess fracture risk in CKD but may underestimate fracture risk in advanced CKD. The trabecular bone score is a measure of grey scale homogeneity obtained from spine DXA, which correlates to trabecular microarchitecture and is an independent risk factor for fracture. Recent data demonstrate the potential utility of the trabecular bone score adjustment of AFR through the FRAX® algorithm in subjects with CKD. Parameters of bone microarchitecture using peripheral quantitative computed tomography (pQCT) or high-resolution pQCT are also able to discriminate fracture status in subjects with CKD. However, there are at present no convincing data that the addition of pQCT or high-resolution pQCT parameters to DXA BMD improves fracture discrimination. More advanced estimates of bone strength derived from measurements of micro-architecture, by QCT-derived finite element analysis may be incorporated into AFR algorithms in the future. © 2017 Asian Pacific Society of Nephrology.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

Science.gov (United States)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient

Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

Energy Technology Data Exchange (ETDEWEB)

Wang, Yuehai [Cardiovascular Department, Liaocheng People’s Hospital of Shandong University, Liaocheng, Shandong 252000 (China); Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lu, Huixia [The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Huang, Ziyang, E-mail: huangziyang666@126.com [Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lin, Huili [Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lei, Zhenmin [Department of OB/GYN, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Chen, Xiaoqing [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Tang, Mengxiong; Gao, Fei; Dong, Mei [The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Li, Rongda [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China); Lin, Ling, E-mail: qzlinl@163.com [Department of Rheumatism and Immunology, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000 (China)

2014-07-18

Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • The spleen weights and glomerular areas were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE{sup −/−} mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE{sup −/−}) mice is a classic model of atherosclerosis. We have found that ApoE{sup −/−} mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared with C57B6/L (B6) mice. However, whether ApoE{sup −/−} mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE{sup −/−}, Fas{sup −/−} and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas{sup −/−} mice, a model of systemic lupus erythematosus (SLE), ApoE{sup −/−} mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE{sup −/−} mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE{sup −/−} mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta.

Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

International Nuclear Information System (INIS)

Wang, Yuehai; Lu, Huixia; Huang, Ziyang; Lin, Huili; Lei, Zhenmin; Chen, Xiaoqing; Tang, Mengxiong; Gao, Fei; Dong, Mei; Li, Rongda; Lin, Ling

2014-01-01

Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE −/− and Fas −/− mice. • The spleen weights and glomerular areas were similar in ApoE −/− and Fas −/− mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE −/− and Fas −/− mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE −/− mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE −/− ) mice is a classic model of atherosclerosis. We have found that ApoE −/− mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared with C57B6/L (B6) mice. However, whether ApoE −/− mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE −/− , Fas −/− and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas −/− mice, a model of systemic lupus erythematosus (SLE), ApoE −/− mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE −/− mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE −/− mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

3D porous architecture of stacks of β-TCP granules compared with that of trabecular bone: a microCT, vector analysis and compression study

Directory of Open Access Journals (Sweden)

Daniel eCHAPPARD

2015-10-01

Full Text Available The 3D arrangement of porous granular biomaterials usable to fill bone defects has received little study. Granular biomaterials occupy 3D space when packed together in a manner that creates a porosity suitable for the invasion of vascular and bone cells. Granules of β-TCP were prepared with either 12.5 or 25g of β-TCP powder in the same volume of slurry. When the granules were placed in a test tube, this produced 3D stacks with a high (HP or low porosity (LP, respectively. Stacks of granules mimic the filling of a bone defect by a surgeon. The aim of this study was to compare the porosity of stacks of β-TCP granules with that of cores of trabecular bone. Biomechanical compression tests were done on the granules stacks. Bone cylinders were prepared from calf tibia plateau, constituted high density (HD blocks. Low density (LD blocks were harvested from aged cadaver tibias. Microcomputed tomography was used on the β-TCP granule stacks and the trabecular bone cores to determine porosity and specific surface. A vector projection algorithm was used to image porosity employing a frontal plane image which was constructed line by line from all images of a microCT stack. Stacks of HP granules had porosity (75.3 ± 0.4% and fractal lacunarity (0.043 ± 0.007 intermediate between that of HD (resp. 69.1 ± 6.4%, p<0.05 and 0.087 ± 0.045, p<0.05 and LD bones (resp. 88.8 ± 1.57% and 0.037 ± 0.014 but exhibited a higher surface density (5.56 ± 0.11 mm2/mm3 vs. 2.06 ± 0.26 for LD, p<0.05. LP granular arrangements created large pores coexisting with dense areas of material. Frontal plane analysis evidenced a more regular arrangement of β-TCP granules than bone trabeculae. Stacks of HP granules represent a scaffold that resembles trabecular bone in its porous microarchitecture.

Clearance of Giardia muris infection in mice deficient in natural killer cells.

OpenAIRE

Heyworth, M F; Kung, J E; Eriksson, E C

1986-01-01

Immunocompetent C57BL/6J mice and beige mice (which are deficient in natural killer cells) were infected with Giardia muris. Both types of mice cleared G. muris infection at similar rates. This observation suggests that clearance of G. muris parasites from the mouse intestine is not mediated by natural killer cells.

Biotechnological approach for systemic delivery of membrane Receptor Activator of NF-κB Ligand (RANKL) active domain into the circulation

Science.gov (United States)

Cappariello, Alfredo; Paone, Riccardo; Maurizi, Antonio; Capulli, Mattia; Rucci, Nadia; Muraca, Maurizio; Teti, Anna

2015-01-01

Deficiency of Receptor Activator of NF-κB Ligand (RANKL) prevents osteoclast formation causing osteopetrosis. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by metalloproteinase 14 (MMP14). We created a bio-device that harbors primary osteoblasts, cultured on 3D hydroxyapatite scaffolds carrying immobilized MMP14 catalytic domain. Scaffolds were sealed in diffusion chambers and implanted in RANKL-deficient mice. Mice received 1 or 2 diffusion chambers, once or twice and were sacrificed after 1 or 2 months from implants. A progressive increase of body weight was observed in the implanted groups. Histological sections of tibias of non-implanted mice were negative for the osteoclast marker Tartrate-Resistant Acid Phosphatase (TRAcP), consistent with the lack of osteoclasts. In contrast, tibias excised from implanted mice showed TRAcP-positive cells in the bone marrow and on the bone surface, these latter morphologically similar to mature osteoclasts. In mice implanted with 4 diffusion chambers total, we noted the highest number and size of TRAcP-positive cells, with quantifiable eroded bone surface and significant reduction of trabecular bone volume. These data demonstrate that our bio-device delivers effective sRANKL, inducing osteoclastogenesis in RANKL-deficient mice, supporting the feasibility of an innovative experimental strategy to treat systemic cytokine deficiencies. PMID:25678116

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women

DEFF Research Database (Denmark)

Cheung, Am; Majumdar, S; Brixen, K

2014-01-01

results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here we report the results of HR-pQCT assessment. 214 postmenopausal women (mean.......64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and BV/TV versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity seen with placebo (treatment difference= -7.7%, p = 0.066). At the distal tibia, odanacatib...... significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal...

Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

Science.gov (United States)

Agarwal, Puneet; Agarwal, Renu

2018-06-14

Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study.

Science.gov (United States)

de Jonge, E A L; Koromani, F; Hofman, A; Uitterlinden, A G; Franco, O H; Rivadeneira, F; Kiefte-de Jong, J C

2017-08-01

We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin and if intake of dietary fibre was high. Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized β (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.

α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.

Directory of Open Access Journals (Sweden)

Jennifer L Hellier

Full Text Available Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7 in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP, an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5-18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21, mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits.

The Inflammatory Response to Social Defeat is Increased in Older Mice

OpenAIRE

Kinsey, Steven G.; Bailey, Michael T.; Sheridan, John F.; Padgett, David A.

2007-01-01

Previous research indicates that repeated social defeat of mice causes increased lymphocyte trafficking to the spleen, elevated proinflammatory cytokine production, and induced glucocorticoid insensitivity in splenocytes. Social defeat also causes increases in anxiety-like behavior. This study investigated whether repeated social defeat results in similar immunoregulatory and behavioral changes in older mice as those seen previously in young adult mice. The data revealed that, regardless of a...

Three-dimensional quantification of structures in trabecular bone using measures of complexity

DEFF Research Database (Denmark)

Marwan, Norbert; Kurths, Jürgen; Thomsen, Jesper Skovhus

2009-01-01

The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three-dimensiona......The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three......-dimensional (3D) imaging of bone challenges the development of data analysis techniques able to assess changes of the 3D microarchitecture of trabecular bone. We introduce an approach based on spatial geometrical properties and define structural measures of complexity for 3D image analysis. These measures...... evaluate different aspects of organization and complexity of 3D structures, such as complexity of its surface or shape variability. We apply these measures to 3D data acquired by high-resolution microcomputed tomography (µCT) from human proximal tibiae and lumbar vertebrae at different stages...

[Cadmium citotoxicity in mice hepatocytes and implications on tropical environments].

Science.gov (United States)

Marcano, Letty; Faría, Clarisa de R; Carruyo, Ingrid; Montiel, Xiomara

2006-06-01

We analyzed phenotypic, structural and ultrastructural alterations induced by Cd+2 in hepatocytes extracted from Swiss Albino mice. Cadmium was given orally in watery solution of CdCl2 during 100 days at concentrations of 50 ppm, 100 ppm and 150 ppm. In controls, distilled water alone was used. The samples were processed with the paraffin inclusion and hematoxilin-eosin coloration techniques for light microscopy. For transmission electron microscopy we used the conventional technique. We found phenotypic (size and weight differences) and physiologic changes (muscular weakness, unrest); at the structural level we noticed loss of trabecular disposition and of lobulillar architecture, lymphocyte agglomeration, vacuolization, dilatation of sinusoid and central vein, among others. The ultrastructural study evidenced alterations coincident with those seen with light microscopy, which were accentuated with the increase of metal concentration: nucleolus with a high number of fibrillar centers (50 ppm); voluminous lipidic drops in the cytoplasm, loose endoplasmic rough reticulum, citoplasmatic vacuolization, altered lisosomes and peroxisomes (100 ppm); contracted nuclei with condensed cromatine, dilatation of intracellular space and mitochondria, and loss of fibrillar areas (150 ppm). Cadmium produces a toxic effect in the hepatic cells; the effect is more severe at higher concentration, leading to cellular necrosis.

Running rescues a fear-based contextual discrimination deficit in aged mice

Directory of Open Access Journals (Sweden)

Melody V. Wu

2015-08-01

Full Text Available Normal aging and exercise exert extensive, often opposing, effects on the dentate gyrus (DG of the hippocampus altering volume, synaptic function, and behaviors. The DG is especially important for behaviors requiring pattern separation—a cognitive process that enables animals to differentiate between highly similar contextual experiences. To determine how age and exercise modulate pattern separation in an aversive setting, young, aged, and aged mice provided with a running wheel were assayed on a fear-based contextual discrimination task. Aged mice showed a profound impairment in contextual discrimination compared to young animals. Voluntary exercise rescued this deficit to such an extent that behavioral pattern separation of aged-run mice was now similar to young animals. Running also resulted in a significant increase in the number of immature neurons with tertiary dendrites in aged mice. Despite this, neurogenesis levels in aged-run mice were still considerably lower than in young animals. Thus, mechanisms other than DG neurogenesis likely play significant roles in improving behavioral pattern separation elicited by exercise in aged animals.

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

Science.gov (United States)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

International Nuclear Information System (INIS)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

Bone ingrowth potential of electron beam and selective laser melting produced trabecular-like implant surfaces with and without a biomimetic coating.

Science.gov (United States)

Biemond, J E; Hannink, G; Verdonschot, N; Buma, P

2013-03-01

The bone ingrowth potential of trabecular-like implant surfaces produced by either selective laser melting (SLM) or electron beam melting (EBM), with or without a biomimetic calciumphosphate coating, was examined in goats. For histological analysis and histomorphometry of bone ingrowth depth and bone implant contact specimens were implanted in the femoral condyle of goats. For mechanical push out tests to analyse mechanical implant fixation specimens were implanted in the iliac crest. The follow up periods were 4 (7 goats) and 15 weeks (7 goats). Both the SLM and EBM produced trabecular-like structures showed a variable bone ingrowth after 4 weeks. After 15 weeks good bone ingrowth was found in both implant types. Irrespective to the follow up period, and the presence of a coating, no histological differences in tissue reaction around SLM and EBM produced specimens was found. Histological no coating was detected at 4 and 15 weeks follow up. At both follow up periods the mechanical push out strength at the bone implant interface was significantly lower for the coated SLM specimens compared to the uncoated SLM specimens. The expected better ingrowth characteristics and mechanical fixation strength induced by the coating were not found. The lower mechanical strength of the coated specimens produced by SLM is a remarkable result, which might be influenced by the gross morphology of the specimens or the coating characteristics, indicating that further research is necessary.

Comparisons of actin filament disruptors and Rho kinase inhibitors as potential antiglaucoma medications

OpenAIRE

Tian, Baohe; Kaufman, Paul L

2012-01-01

Dynamics of the actin cytoskeleton in the trabecular meshwork play a crucial role in the regulation of trabecular outflow resistance. The actin filament disruptors and Rho kinase inhibitors affect the dynamics of the actomyosin system by either disrupting the actin filaments or inhibiting the Rho kinase-activated cellular contractility. Both approaches induce similar morphological changes and resistance decreases in the trabecular outflow pathway, and thus both have potential as antiglaucoma ...

Men and mice: Relating their ages.

Science.gov (United States)

Dutta, Sulagna; Sengupta, Pallav

2016-05-01

Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered pancreatic growth and insulin secretion in WSB/EiJ mice.

Directory of Open Access Journals (Sweden)

Maggie M Ho

Full Text Available These data suggest that insulin secretion in WSB mice is blunted specifically in vivo, either due to a reduced insulin requirement and/or due to factors that are absent or destroyed in vitro. These studies also highlight the role of post-natal growth in determining adult β-cell mass. Mice are important animal models for the study of metabolic physiology and the genetics of complex traits. Wild-derived inbred mouse strains, such as WSB/EiJ (WSB, are unrelated to the commonly studied mouse strains and are valuable tools to identify novel genes that modify disease risk. We have previously shown that in contrast to C57BL/6J (B6 mice, WSB mice fed a high fat diet do not develop hyperinsulinemia or insulin resistance, and had nearly undetectable insulin secretion in response to an intraperitoneal glucose challenge. As hyperinsulinemia may drive obesity and insulin resistance, we examined whether defects in β-cell mass or function could contribute to the low insulin levels in WSB mice. In young WSB mice, β-cell mass was similar to B6 mice. However, we found that adult WSB mice had reduced β-cell mass due to reduced pancreatic weights. Pancreatic sizes were similar between the strains when normalized to body weight, suggesting their pancreatic size is appropriate to their body size in adults, but overall post-natal pancreatic growth was reduced in WSB mice compared to B6 mice. Islet architecture was normal in WSB mice. WSB mice had markedly increased insulin secretion from isolated islets in vitro. These data suggest that insulin secretion in WSB mice is blunted specifically in vivo, either due to a reduced insulin requirement and/or due to factors that are absent or destroyed in vitro. These studies suggest that WSB mice may provide novel insight into mechanisms regulating insulin secretion and also highlight the role of post-natal growth in determining adult β-cell mass.

Effect of ultraviolet irradiation on mast cell-deficient W/Wv mice

International Nuclear Information System (INIS)

Ikai, K.; Danno, K.; Horio, T.; Narumiya, S.

1985-01-01

The effect of UV irradiation on the skin was investigated in (WB-W/+) X (C57BL/6J-Wv/+)F1-W/Wv mice, which are genetically deficient in tissue mast cells. Their congenic littermates (+/+) and normal albino mice (ICR or BALB/c) were used as controls. Mice were irradiated with 500 mJ/cm2 of UVB and the increment of ear thickness was measured before and 6, 12, and 24 h after irradiation. Ear swelling in W/Wv mice at 12 and 24 h after irradiation was significantly smaller than that in +/+ and ICR mice. In contrast, the number of sunburn cells formed 24 h after UVB irradiation (200 or 500 mJ/cm2) was similar in W/Wv, +/+ and ICR mice. On the other hand, when mice were treated with 8-methoxy-psoralen (0.5%) plus UVA irradiation (4 J/cm2) (topical PUVA), ears of W/Wv and BALB/c mice, which were both white in color, were thickened similarly 72 h after treatment, but less swelling was observed in +/+ mice, which were black in skin color. The amount of prostaglandin D2 (PGD2) in ears, determined by radioimmunoassay specific for PGD2, was elevated 3-fold in +/+ and ICR mice at 3 h after irradiation with 500 mJ/cm2 of UVB in comparison with basal level without irradiation. However, such elevation was not observed in W/Wv mice. These results suggest that mast cells play an important role in UVB-induced inflammation, and PGs from mast cells are responsible at least in part for the development of this reaction. However, neither mast cells nor PGs contribute to the sunburn cell formation and ear swelling response by PUVA treatment

Effect of ethanol on placenta and liver of mice

International Nuclear Information System (INIS)

Tarachand, U.; Eapen, Jacob

1977-01-01

Chronic ingestion of ethanol in drinking water for 15 days induces fatty liver in non-pregnant female mice. A similar regimen fails to produce the same effect in liver and placenta of pregnant mice. In vivo incorporation of 14 C-chlorella protein hydrolysate into hepatic proteins, however, is impaired in both the pregnant and the non-pregnant mice following ethanol treatment. Placental and foetal liver protein syntheses remain unaffected by the treatment. A single intraperitoneal dose of ethanol in fed and fasted non-pregnant mice elicits a differential response with respect to incorporation of the labelled precursor. The results are discussed with reference to the apparent metabolic alterations due to pregnancy. (author)

Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

Science.gov (United States)

Acevedo, Summer F.; Raber, Jacob

2011-01-01

Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

Science.gov (United States)

Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

Radioprotection by polyethylene glycol-protein complexes in mice

International Nuclear Information System (INIS)

Gray, B.H.; Stull, R.W.

1983-01-01

Polyethylene glycol of about 5000 D was activated with cyanuric chloride, and the activated compound was complexed to each of three proteins. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase were each radioprotectants when administered prophylactically to female B6CBF1 mice before irradiation. The dose reduction factor for these mice was 1.2 when 5000 units of polyethylene glycol-catalase was administered before 60 Co irradiation. Female B6CBF1 mice administered prophylactic intravenous injections of catalase, polyethylene glycol-albumin, or heat-denatured polyethylene glycol-catalase had survival rates similar to phosphate-buffered saline-injected control mice following 60 Co irradiation. Polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase have radioprotective activity in B6CBF1 mice, which appears to depend in part on enzymatic activities of the complex. However, no radioprotective effect was observed in male C57BL/6 mice injected with each polyethylene glycol-protein complex at either 3 or 24 hr before irradiation. The mechanism for radioprotection by these complexes may depend in part on other factors

Temporal stability of novelty exploration in mice exposed to different open field tests.

Science.gov (United States)

Kalueff, Allan V; Keisala, Tiina; Minasyan, Anna; Kuuslahti, Marianne; Tuohimaa, Pentti

2006-03-01

We investigated behavioural activity and temporal distribution (patterning) of mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain were subjected in parallel to three different OF arenas (Experiment 1), two different OF arenas in two trials (Experiment 2) or two trials of the same OF test (Experiment 3). Overall, mice demonstrated a high degree of similarity in the temporal profile of novelty-induced horizontal and vertical exploration (regardless of the size, colour and shape of the OF), which remained stable in subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c-S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic background), again showing strikingly similar temporal patterns of their OF exploration, despite marked behavioural strain differences in anxiety and activity. These results suggest that mice are characterised by stability of temporal organization of their exploration in different OF novelty situations.

Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice.

Science.gov (United States)

Mannix, Rebekah C; Zhang, Jimmy; Park, Juyeon; Zhang, Xuan; Bilal, Kiran; Walker, Kendall; Tanzi, Rudolph E; Tesco, Giuseppina; Whalen, Michael J

2011-01-01

The apolipoprotein E4 (APOE4) gene leads to increased brain amyloid beta (Aβ) and poor outcome in adults with traumatic brain injury (TBI); however, its role in childhood TBI is controversial. We hypothesized that the transgenic expression of human APOE4 worsens the outcome after controlled cortical impact (CCI) in adult but not immature mice. Adult and immature APOE4 mice had worse motor outcome after CCI (P<0.001 versus wild type (WT)), but the Morris water maze performance was worse only in adult APOE4 mice (P=0.028 at 2 weeks, P=0.019 at 6 months versus WT), because immature APOE4 mice had performance similar to WT for up to 1 year after injury. Brain lesion size was similar in adult APOE4 mice but was decreased (P=0.029 versus WT) in injured immature APOE4 mice. Microgliosis was similar in all groups. Soluble brain Aβ(40) was increased at 48 hours after CCI in adult and immature APOE4 mice and in adult WT (P<0.05), and was dynamically regulated during the chronic period by APOE4 in adults but not immature mice. The data suggest age-dependent effects of APOE4 on cognitive outcome after TBI, and that therapies targeting APOE4 may be more effective in adults versus children with TBI.

Assessment of circumferential angle-closure by the iris-trabecular contact index with swept-source optical coherence tomography.

Science.gov (United States)

Baskaran, Mani; Ho, Sue-Wei; Tun, Tin A; How, Alicia C; Perera, Shamira A; Friedman, David S; Aung, Tin

2013-11-01

To evaluate the diagnostic performance of the iris-trabecular contact (ITC) index, a measure of the degree of angle-closure, using swept-source optical coherence tomography (SSOCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) in comparison with gonioscopy. Prospective observational study. A total of 108 normal subjects and 32 subjects with angle-closure. The SSOCT 3-dimensional angle scans, which obtain radial scans for the entire circumference of the angle, were performed under dark conditions and analyzed using customized software by a single examiner masked to the subjects' clinical details. The ITC index was calculated as a percentage of the angle that was closed on SSOCT images. First-order agreement coefficient (AC1) statistics and area under the receiver operating characteristic curve (AUC) analyses were performed for angle-closure on the basis of the ITC index in comparison with gonioscopy. Angle-closure on gonioscopy was defined as nonvisibility of posterior trabecular meshwork for at least 2 quadrants. Agreement of the ITC index with gonioscopically defined angle-closure was assessed using the AC1 statistic. Study subjects were predominantly Chinese (95.7%) and female (70.7%), with a mean age of 59.2 (standard deviation, 8.9) years. The median ITC index was 15.24% for gonioscopically open-angle eyes (n = 108) and 48.5% for closed-angle eyes (n = 32) (P = 0.0001). The agreement for angle-closure based on ITC index cutoffs (>35% and ≥50%) and gonioscopic angle-closure was 0.699 and 0.718, respectively. The AUC for angle-closure detection using the ITC index was 0.83 (95% confidence interval, 0.76-0.89), with an ITC index >35% having a sensitivity of 71.9% and specificity of 84.3%. The ITC index is a summary measure of the circumferential extent of angle-closure as imaged with SSOCT. The index had moderate agreement and good diagnostic performance for angle-closure with gonioscopy as the reference standard. Copyright © 2013 American Academy of

Characterization of cellular solids in Ti6Al4V for orthopaedic implant applications: Trabecular titanium.

Science.gov (United States)

Marin, E; Fusi, S; Pressacco, M; Paussa, L; Fedrizzi, L

2010-07-01

EBM (Electron Beam Melting) technology can be used successfully to obtain cellular solids in metallic biomaterials that can greatly increase osseointegration in arthroprothesis and at the same time maintain good mechanical properties. The investigated structures, called Trabecular Titanium, usually cannot be obtained by traditional machining. Two samples: (A) with a smaller single cell area and, (B) with a bigger single cell area, were produced and studied in this project. They have been completely characterized and compared with the results in similar literature pertinent to Ti6Al4V EBM structures. Relative density was evaluated using different methods, the mean diameter of the open porosities was calculated by Scanning Electron Microscope images; the composition was evaluated using Energy-Dispersive X-Ray Spectroscopy; the microstructure (alpha-beta) was investigated using chemical etching and, the mechanical proprieties were investigated using UMTS. The mean porosity values resulted comparable with spongy bone (63% for A and 72% for B). The mean diameter of the single porosity (650 mum for A and 1400 mum for B) resulted compatible with the osseointegration data from the literature, in particular for sample A. The Vickers micro-hardness tests and the chemical etching demonstrated that the structure is fine, uniform and well distributed. The mechanical test proved that sample (A) was more resistant than sample (B), but sample (B) showed an elastic modulus almost equal to the value of spongy bone. The results of this study suggest that the two Ti6Al4V cellular solids can be used in biomedical applications to promote osseointegration demonstrating that they maybe successfully used in prosthetic implants. Additional implant results will be published in the near future. Copyright 2010 Elsevier Ltd. All rights reserved.

Contribution of non-immune phagocytes to protection of mice against Vibrio cholerae

International Nuclear Information System (INIS)

Tsuru, Sumiaki; Seno, Masao; Tsuchiya, Choji; Noritake, Masayuki; Wasada, Kazunori

1980-01-01

Bacterial kinetics of Vibrio cholerae 569B in the local infection of mice was examined after the γ-ray-irradiation or the treatment with carrageenan. In the control mice, bacterial number decreased exponentially. In the mice treated with carrageenan gave similar tendency. In the irradiated mice, however, decrease in bacterial number was not as significant and the clearance was never observed. From these results, it is concluded that the protection against V. cholerae local infection depends mainly on polymorphonuclear cells in the early phase. (author)

SPILANTHES ACMELLA AND PHYSICAL EXERCISE INCREASED TESTOSTERONE LEVELS AND OSTEOBLAST CELLS IN GLUCOCORTICOID-INDUCED OSTEOPOROSIS MALE MICE

Directory of Open Access Journals (Sweden)

Hening Laswati

2015-08-01

Full Text Available Background: Glucocorticoid-induced osteoporosis is leading cause of secondary osteoporosis by decreasing formation activity and increasing resorption activity. Spilanthes acmella, is one of Indonesia medicinal plants that contain of polyphenol and flavonoids. Previously in vitro study showed that buthanol and water fraction from this plant have increased alkaline phosphatase that known as marker of bone formation. The objective of this study to analyze the effect of Spilanthes acmella  and physical exercise in increasing testosterone and  osteoblast cells of femoral’s trabecular glucocorticoid-induced osteoporosis male mice. Method: This study using a posttest control group design, 36 male healthy mice (5 months old  were randomizely devided into 6 groups, there are : 1.Healthy control group (without induction dexamethaxone, 2.Osteoporosis groups (induction with dexamethaxone without treatment, 3.Positive control receive suspension alendronat, 4.70% Ethanol extract of Spilanthes acmella group, 5.Combination group of 70% extract ethanol of Spilanthes acmella and exercise, and 6.Exercise group  (walking using mice treadmill 10m/minute, 5-12 minutes 3 times a week. All of the intervention were given for 4 weeks. The serum levels of testosterone were determined using  immunoserology (ELISA and osteoblast cells were determined histomorphometry by light microscopy.  All statistical test were carried out using SPSS 23 and statistical significance was  set at p<0.05 for all analysis. The testosterone levels  between group were compared using Mann-Whitney test and osteoblast cells between group were compared with multiple comparison. Results: It showed that the alendronate group, combination group and the exercise group increasing testosterone level (p<0.05 from that osteoporotic group. There were also increasing osteoblast cells (p<0.05 in the alendronate group and combination group. There was no correlation between testosterone level and

Large-angle coherent/Compton scattering method for measurement in vitro of trabecular bone mineral concentration

International Nuclear Information System (INIS)

Gigante, G.E.; Sciuti, S.

1985-01-01

In this paper, experiments and related theoretical deductions on coherent/Compton scattering of 59.5-keV Am241 gamma line by bonelike materials are described. In particular, the authors demonstrate that a photon scattering mineralometer (PSM) can attain the best working conditions when it operates in a backscattering geometry mode. In fact, the large scattering angle they chose, theta = 135 degrees, allowed them to assemble a very compact source-detector device. Further, the relative sensitivity at 135 degrees turns out to be congruent to 1.7 and congruent to 6 times bigger than at 90 degrees and 45 degrees, respectively. The performances of the theta = 135 degrees PSM were experimentally investigated; i.e., in a measuring time of 10(3) s, a congruent to 5% statistical precision for bonelike materials, such as K 2 HPO 4 -water solutions, was obtained. The large-angle PSM device seems to be very promising for trabecular bone mineral density measurements in vivo in peripheral anatomic sites

Clopidogrel (Plavix®), a P2Y(12) receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo

DEFF Research Database (Denmark)

Syberg, Susanne; Brandao-Burch, Andrea; Patel, Jessal J

2012-01-01

Clopidogrel (Plavix®), a selective P2Y(12) receptor antagonist, is widely prescribed to reduce the risk of heart attack and stroke and acts via the inhibition of platelet aggregation. Accumulating evidence now suggests that extracellular nucleotides, signalling through P2 receptors, play...... a significant role in bone, modulating both osteoblast and osteoclast function. In this study, we investigated the effects of clopidogrel treatment on (1) bone cell formation, differentiation and activity in vitro; and, (2) trabecular and cortical bone parameters in vivo. P2Y(12) receptor expression...

Social factors modulate restraint stress induced hyperthermia in mice.

Science.gov (United States)

Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Energy metabolism in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-05-01

Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (PBPH/2J compared with BPN/3J mice (PBPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

Aged mice have increased inflammatory monocyte concentration ...

Indian Academy of Sciences (India)

monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

Distribution of copper-64 in control mice and in mice bearing ascitic Krebs tumor cells

International Nuclear Information System (INIS)

Apelgot, S.; Coppey, J.; Grisvard, J.; Guille, E.; Sissoeeff, I.

1981-01-01

Three to 20 hr after an i.p. injection of 64 Cu (half-life, 12.8 hr) into mice bearing Krebs ascites cells, a high amount of the radioisotope was recovered in the ascites cells themselves. In the control group, the radioisotope was mainly present in the liver. Similar amounts of 64 Cu were recovered in regenerating as well as in normal liver, whereas in the liver of mice bearing ascites cells, this amount was lower by 40 to 50% regardless of the ascitic volume. Thus, the copper metabolism seems to be disturbed at the hepatic level in mice bearing ascites cells. The distribution of 64 Cu was 'analyzed in DNA, RNA, and proteins from cellular lysates fractionated by CsCl gradient. There was a uniform pattern of distribution in the macromolecules from ascites cells, while 64 Cu' was preferentially associated with the protein fraction from liver. Further experiments indicated that, in vivo, 64 Cu was bound to the DNA of ascites cells

Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Gustafsson, Åsa, E-mail: asa.gustafsson@foi.se [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bergström, Ulrika [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Organismal Biology, Uppsala University, SE-751 Uppsala (Sweden); Ågren, Lina [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Österlund, Lars [Dept of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 Uppsala (Sweden); Sandström, Thomas [Dept of Public Health and Clinical Medicine, Umeå University (Sweden); Bucht, Anders [Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå (Sweden); Dept of Public Health and Clinical Medicine, Umeå University (Sweden)

2015-10-01

The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. - Highlights: • Hematite NPs induce differential responses in airways of healthy and allergic mice. • Hematite induced an airway inflammation in healthy mice. • Hematite induced cellular reduction in the alveolus and lymph nodes of allergic mice. • Cell death is possible due to extensive pro-oxidative environment in allergic mice. • It is important to include sensitive individuals when valuing health effects of NPs.

3D histomorphometric quantification of trabecular bones by computed microtomography using synchrotron radiation.

Science.gov (United States)

Nogueira, L P; Braz, D; Barroso, R C; Oliveira, L F; Pinheiro, C J G; Dreossi, D; Tromba, G

2010-12-01

Conventional bone histomorphometry is an important method for quantitative evaluation of bone microstructure. X-ray computed microtomography is a non-invasive technique, which can be used to evaluate histomorphometric indices in trabecular bones (BV/TV, BS/BV, Tb.N, Tb.Th, Tb.Sp). In this technique, 3D images are used to quantify the whole sample, differently from the conventional one, in which the quantification is performed in 2D slices and extrapolated for 3D case. In this work, histomorphometric quantification using synchrotron 3D X-ray computed microtomography was performed to quantify the bone structure at different skeletal sites as well as to investigate the effects of bone diseases on quantitative understanding of bone architecture. The images were obtained at Synchrotron Radiation for MEdical Physics (SYRMEP) beamline, at ELETTRA synchrotron radiation facility, Italy. Concerning the obtained results for normal and pathological bones from same skeletal sites and individuals, from our results, a certain declining bone volume fraction was achieved. The results obtained could be used in forming the basis for comparison of the bone microarchitecture and can be a valuable tool for predicting bone fragility. Copyright © 2010 Elsevier Ltd. All rights reserved.

Zinc metabolism in genetically obese (ob/ob) mice

International Nuclear Information System (INIS)

Kennedy, M.L.; Failla, M.L.

1987-01-01

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 mumol 65 Zn by stomach tube the apparent absorption of 65 Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65 Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65 Zn by obese mice food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum--fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65 Zn, respectively. In contrast, the rate of 65 Zn excretion 2-6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65 Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice

Linkage disequilibrium in wild mice.

Directory of Open Access Journals (Sweden)

Cathy C Laurie

2007-08-01

Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice.

Science.gov (United States)

Carow, Berit; Gao, Yu; Terán, Graciela; Yang, Xuexian O; Dong, Chen; Yoshimura, Akihiko; Rottenberg, Martin E

2017-12-01

CISH gene has been associated with increased susceptibility to human tuberculosis. We found that cish -/- mice had higher M. tuberculosis load in spleens and lungs up to 2.5 weeks after infection but not later compared to controls. Cish mRNA levels were increased in lungs at early and late time points after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in lungs were reduced early after infection of cish -/- mice. The transfer of cish -/- and control T cells conferred rag1 -/- mice similar protection to infection with M. tuberculosis. Macrophages showed increased cish mRNA levels after M. tuberculosis infection in vitro. However, mycobacterial uptake and growth in cish -/- and control macrophages was similar. Thus, we here show that CISH mediates control of M. tuberculosis in mice early after infection via regulation of innate immune mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropathology in mice expressing mouse alpha-synuclein.

Directory of Open Access Journals (Sweden)

Claus Rieker

Full Text Available α-Synuclein (αSN in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN, which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occurred in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

Directory of Open Access Journals (Sweden)

Chise Tateno

Full Text Available We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID. We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

Science.gov (United States)

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-Ichiro; Jishage, Kou-Ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for

Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice

Directory of Open Access Journals (Sweden)

Portugal L.R.

2006-01-01

Full Text Available Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. The proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. Although this effect was demonstrated in vitro, its relevance in vivo is still controversial. Furthermore, few studies have investigated the role of lactobacilli in atherogenesis. The aim of the present study was to determine the effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein E (apo E knock-out (KO mice. For this purpose, Swiss/NIH germ-free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol excretion in germ-free mice, which was not associated with changes in blood or liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. In conclusion, these results suggest that, although L. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo E KO mice.

Similar effectiveness of Fab and F(ab')2 antivenoms in the neutralization of hemorrhagic activity of Vipera berus snake venom in mice

OpenAIRE

Lomonte, Bruno; León Montero, Guillermo; Hanson, Lars Ake

1996-01-01

The ability of two antivenoms to Vipera spp., consisting of Fab (Therapeutic Antibodies), or of F(ab′)2 (Zagreb Institute of Immunology) antibody fragments, to neutralize the hemorrhagic activity of Vipera berus snake venom in mice, was compared. First, the neutralizing potency was determined by in vitro preincubation of venom and antivenom, followed by intradermal injection into mice and subsequent measurement of the hemorrhagic area. Both antivenoms had the same anti-hemorrhagic potency, in...

Mice lacking mPGES-1 are resistant to lithium-induced polyuria.

Science.gov (United States)

Jia, Zhanjun; Wang, Haiping; Yang, Tianxin

2009-12-01

Cyclooxygenase-2 activity is required for the development of lithium-induced polyuria. However, the involvement of a specific, terminal prostaglandin (PG) isomerase has not been evaluated. The present study was undertaken to assess lithium-induced polyuria in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1). A 2-wk administration of LiCl (4 mmol.kg(-1).day(-1) ip) in mPGES-1 +/+ mice led to a marked polyuria with hyposmotic urine. This was associated with elevated renal mPGES-1 protein expression and increased urine PGE(2) excretion. In contrast, mPGES-1 -/- mice were largely resistant to lithium-induced polyuria and a urine concentrating defect, accompanied by nearly complete blockade of high urine PGE(2) and cAMP output. Immunoblotting, immunohistochemistry, and quantitative (q) RT-PCR consistently detected a significant decrease in aquaporin-2 (AQP2) protein expression in both the renal cortex and medulla of lithium-treated +/+ mice. This decrease was significantly attenuated in the -/- mice. qRT-PCR detected similar patterns of changes in AQP2 mRNA in the medulla but not in the cortex. Similarly, the total protein abundance of the Na-K-2Cl cotransporter (NKCC2) in the medulla but not in the cortex of the +/+ mice was significantly reduced by lithium treatment. In contrast, the dowregulation of renal medullary NKCC2 expression was significantly attenuated in the -/- mice. We conclude that mPGES-1-derived PGE(2) mediates lithium-induced polyuria likely via inhibition of AQP2 and NKCC2 expression.

Outcomes of combined trabecular micro-bypass and phacoemulsification in a predominantly Hispanic patient population

Directory of Open Access Journals (Sweden)

Gallardo MJ

2016-10-01

Full Text Available Mark J Gallardo,1,2 Richard A Supnet,1 Jane Ellen Giamporcaro,3 Dana M Hornbeak3 1El Paso Eye Surgeons, PA, El Paso, 2Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 3Division of Clinical Research and Medical Affairs, Glaukos Corporation, Laguna Hills, CA, USA Purpose: The purpose of this study was to evaluate intraocular pressure (IOP and topical ocular hypotensive medication burden at 12 months postoperatively in a predominantly Hispanic patient population with primary open-angle glaucoma each implanted with one trabecular micro-bypass stent during cataract surgery.Methods: This was a retrospective, consecutive case series. The main objective was to assess reduction of IOP and/or medication burden in all eyes at the 12-month postoperative exam. A secondary objective was to assess outcomes in 3 subgroups, distinguished preoperatively by IOP control and by medication burden (suboptimal or maximum therapy and with different treatment goals. Group 1 had medication-controlled IOP and goal to reduce medications while maintaining IOP control (n=65; Group 2 had uncontrolled IOP on ≤2 medications and goal to reduce IOP and maintain/reduce medication burden (n=31; and Group 3 had uncontrolled IOP on ≥3 medications and goal to reduce IOP and avoid filtering surgery (n=38. Evaluations included IOP, medication use, cup-to-disc ratio, visual fields, complications, and interventions. One hundred subjects (134 eyes have been followed for 12 months.Results: Most patients (80% were Hispanic and had moderate or severe glaucoma (87%. At 12 months, mean IOP reduced to 12.9 mmHg vs 16.5 mmHg preoperatively; 92% had an IOP ≤15 mmHg at 12 months (99% had ≤18 mmHg. Mean medication burden had decreased to 0.9 vs 2.3 preoperatively. At the 12-month time point, 94% of all eyes achieved their predefined treatment goal of reduced IOP and/or medications. Reductions in medication burden for Group 1, and

A coherent/Compton scattering method employing an x-ray tube for measurement of trabecular bone mineral content

International Nuclear Information System (INIS)

Puumalainen, P.; Uimarihuhta, A.; Olkkonen, H.

1982-01-01

Results showed that the x-ray generator could be used as a radiation source in the coherent/Compton scattering method of measuring trabecular bone mineral content. The quasimonoenergetic x-ray beam was produced from the continuous bremsstrahlung radiation with the aid of a spectral filter. Of the two measuring arrangements that were tested, the semiconductor detector geometry appeared to give distinctly more reproducible results than the two NaI detector system. However, to improve the counting efficiency of the coherent radiation, the 'coherent' NaI detector could be replaced by a bore-through scintillation probe (bore diameter about 10mm). By placing the x-ray fluorescence target inside the bore, the yield would be considerably higher. The present method is suitable for TBMC measurements of small animal and human peripheral bones. Errors are discussed in relation to increase of bone size. (U.K.)

Dominant lethal mutations in male mice fed γ-irradiated diet

International Nuclear Information System (INIS)

Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

1975-01-01

Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

Science.gov (United States)

Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

2016-02-01

Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethanol self-administration in serotonin transporter knockout mice: unconstrained demand and elasticity.

Science.gov (United States)

Lamb, R J; Daws, L C

2013-10-01

Low serotonin function is associated with alcoholism, leading to speculation that increasing serotonin function could decrease ethanol consumption. Mice with one or two deletions of the serotonin transporter (SERT) gene have increased extracellular serotonin. To examine the relationship between SERT genotype and motivation for alcohol, we compared ethanol self-administration in mice with zero (knockout, KO), one (HET) or two copies (WT) of the SERT gene. All three genotypes learned to self-administer ethanol. The SSRI, fluvoxamine, decreased responding for ethanol in the HET and WT, but not the KO mice. When tested under a progressive ratio schedule, KO mice had lower breakpoints than HET or WT. As work requirements were increased across sessions, behavioral economic analysis of ethanol self-administration indicated that the decreased breakpoint in KO as compared to HET or WT mice was a result of lower levels of unconstrained demand, rather than differences in elasticity, i.e. the proportional decreases in ethanol earned with increasing work requirements were similar across genotypes. The difference in unconstrained demand was unlikely to result from motor or general motivational factors, as both WT and KO mice responded at high levels for a 50% condensed milk solution. As elasticity is hypothesized to measure essential value, these results indicate that KO value ethanol similarly to WT or HET mice despite having lower break points for ethanol. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

Science.gov (United States)

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice

Science.gov (United States)

Holmes, Greg; Bromage, Timothy G.; Basilico, Claudio

2011-01-01

We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1α1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo. PMID:21703370

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

Directory of Open Access Journals (Sweden)

Ramesh Chennupati

Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

Calcium and phosphorus concentrations and the calcium/phosphorus ratio in trabecular bone from the femoral neck of healthy humans as determined by neutron activation analysis

International Nuclear Information System (INIS)

Zaichick, Vladimir; Tzaphlidou, Margaret

2003-01-01

The Ca and P concentrations as well as the Ca/P ratio were estimated in intact trabecular bone samples from the femoral neck of healthy humans, 34 women and 44 men, aged from 15 to 55 years, using instrumental neutron activation analysis. The mean values (M±SD) for the investigated parameters (on a dry-weight basis) were: 12.1±3.0%, 5.94±1.71%, 2.07±0.25 and 10.9±2.5%, 5.30±1.23%, 2.07±0.22 for females and males, respectively. A statistically significant (p≤0.05) decrease of Ca concentration with age was found only for males while the P concentration and the Ca/P ratio were not affected by age. No statistically significant sex-related differences were observed in any of the parameters. The mean values for Ca, P and the Ca/P ratio lay close to the median of the very wide range of published data. The individual variation for the Ca/P ratio in trabecular bone from the healthy human femoral neck was lower than those for Ca and P separately. This suggests that the specificity of the Ca/P ratio is better than that of Ca and P concentrations and may be more reliable for the diagnosis of bone disorders

Analysis of mice radiosensitivity depending on age

International Nuclear Information System (INIS)

Bogatyrev, A.V.; Timoshenko, S.I.; Nikanorova, N.G.; Sverdlov, A.G.

1979-01-01

In order to elucidate mechanisms of age variations in radiosensitivity of mice a study was made of the sensitivity of in vitro irradiated bone marrow stem cells, taken from animals of different age, and postradiation recovery of leukocyte content of peripheral blood and cellularity of bone marrow and spleen. Using the method of spleen colonies similar affections were revealed in bone marrow cells of animals of different age. The degree of recovery of the hemopoietic cell pool was significantly lower in newborn mice than in adults after exposure to a dose (LDsub(50/30)) equally effective with respect to mortality

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

Visibility of trabecular meshwork by standard and polarization-sensitive optical coherence tomography

Science.gov (United States)

Yasuno, Yoshiaki; Yamanari, Masahiro; Kawana, Keisuke; Miura, Masahiro; Fukuda, Shinichi; Makita, Shuichi; Sakai, Shingo; Oshika, Tetsuro

2010-11-01

Polarization-sensitive optical coherence tomography (PS-OCT) is known to be advantageous because of its additional tissue-specific contrast of the anterior eye. So far, this advantage has been shown only qualitatively. We evaluate the improved visibility afforded by 3-D PS corneal and anterior eye segment OCT (PS-CAS-OCT) in visualizing the trabecular meshwork (TM) based on statistical evidences. A total of 31 normal subjects participated in this study. The anterior eye segments of both the eyes of the subjects are scanned using a custom-made PS-CAS-OCT and the standard-scattering OCT (S-OCT) and polarization-sensitive phase-retardation OCT (P-OCT) images are obtained. Three graders grade the visibility of the TM using a four-leveled grading system. The intergrader agreement, intermodality differences, and interquadrant dependence of visibility are statistically examined. All three of three combinations of graders show substantial agreement in visibility with P-OCT (ρ = 0.74, 0.70, and 0.68, Spearman's correlation), while only one of three shows substantial agreement with S-OCT (ρ = 0.72). Significant dependence of the visibility on the modality (S-OCT versus P-OCT) and quadrants are found by the analysis of variance. A subsequent Wilcoxon signed-rank test reveals significantly improved visibility. PS-CAS-OCT may become a useful tool for screening angle-closure glaucoma.

TRABECULAR BONE SCORE – A NON-INVASIVE ANALYTICAL METHOD TO EVALUATE BONE QUALITY BASED ON ROUTINE DUAL-ENERGY ABSORPTIOMETRY. PERSPECTIVES OF ITS USE IN CLINICAL PRACTICE

Directory of Open Access Journals (Sweden)

T. T. Tsoriev

2016-01-01

Full Text Available Two-dimensional dual-energy X-ray absorptiometry (DXA, osteodensitometry is currently considered as the gold standard for diagnosis of osteoporosis. However, despite good operational characteristics, this type of investigation cannot help to assess bone microarchitecture and the degree of its derangement in osteoporosis. Therefore, trabecular bone score (TBS has been developed as a  non-invasive method of indirect description of bone microarchitecture based on data derived from a  standard DXA of the lumbar spine. Not being a direct mapping of the physical measurements of trabecular microarchitecture, TBS nevertheless shows a positive correlation with quantitative values obtained from micro-computed tomography and high resolution peripheral quantitative computed tomography, i.e. with the bone volume fraction, junction density, trabecular numbers and their disintegration. There is also an association between the ability of the bone tissue to resist stress in experimental studies ex vivo and TBS measurement. Due to TBS, there is a possibility to detect bone microarchitecture impairment even in individuals with normal bone mineral density (BMD, i.e. higher TBS values correlate with improved bone microstructure, whereas a  reduced TBS shows its deterioration. Limitation of TBS use are primarily related to the DXA image quality: image faults caused either by technical reasons or by too low or too high body mass index can lead to an overestimation/underestimation of the index. Assessment of the lumbar TBS has been repeatedly performed in cross-sectional and prospective studies in representative patient samples (mainly postmenopausal women and significant numbers of healthy subjects, and proved to be a predictor (independent of BMD of fracture risk. An evaluation of the possibility to use TBS for early diagnosis of secondary osteoporosis (related to various endocrine disorders  would be of great interest, as BMD, as known from clinical

Cadmium cytotoxicity in albino mice hepatocytes and its possible implications on tropical environments

International Nuclear Information System (INIS)

Marcano, Letty; Carruyo, Ingrid; Montiel, Xiomara; Faria, Clarisa de R.

2006-01-01

Analyzed phenotypic, structural and ultrastructural alterations induced by Cd +2 in hepatocytes extracted from Swiss Albino mice. Cadmium was given orally in watery solution of CdCl 2 during 100 days at concentrations of 50 ppm, 100 ppm and 150 ppm. In controls, distilled water alone was used. The samples were processed with the paraffin inclusion and hematoxylin-eosin coloration techniques for light microscopy. The conventional technique was used for transmission electron microscopy . Phenotypic (size and weight differences) and physiologic changes (muscular weakness, unrest) were found; at the structural level it was noticed loss of trabecular disposition and of lobular architecture, lymphocyte agglomeration, vacuolisation, dilatation of sinusoid and central vein, among others. The ultrastructural study evidenced alterations coincident with those seen with light microscopy, which were accentuated with the increase of metal concentration: nucleolus with a high number of fibrillar centers (50 ppm); voluminous lipidic drops in the cytoplasm, loose endoplasmic rough reticulum, cytoplasmic vacuolisation, altered lysosomes and peroxisomes (100 ppm); contracted nucleis with condensed chromatin, dilatation of intracellular space and mitochondria, and loss of fibrillar areas (150 ppm). Cadmium produces a toxic effect in the hepatic cells; the effect is more severe at higher concentration, leading to cellular necrosis. (author) [es

A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

Science.gov (United States)

Gerard-O'Riley, Rita L.; Acton, Dena; McQueen, Amie K.; Strobel, Isabel E.; Witcher, Phillip C.; Feng, Jian Q.; Econs, Michael J.

2017-01-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. PMID:28005411

Initial clinical experience with the trabecular micro-bypass stent in patients with glaucoma.

Science.gov (United States)

Spiegel, Detlev; Wetzel, Wolfgang; Haffner, David S; Hill, Richard A

2007-01-01

This study was undertaken to evaluate the efficiency of a trabecular micro-bypass stent designed to allow direct aqueous drainage from the anterior chamber into Schlemm's canal in patients with glaucoma. In this prospective case series of 6 patients with open-angle glaucoma, the microstent was inserted ab interno under local anesthesia in an ophthalmic operating room. Patients were seen postoperatively at 1 to 2 d, 1 wk, and 1, 2, 6, and 12 mo. All stents were successfully placed within Schlemm's canal. Mean intraocular pressure (IOP) at preoperative baseline was 20.2+/-6.3 mm Hg (range, 14-31 mm Hg). Mean IOP decreased during the immediate postoperative period to approximately 12 to 13 mm Hg and was stabilized at 14 to 15 mm Hg with reduction of medication throughout 1 y of follow-up. No major complications occurred. According to observations reported in this feasibility study, the microstent was effective in reducing IOP and in decreasing the number of glaucoma medications required to control IOP. Implantation procedures were safe, and stents remained in place throughout the follow-up period. None of the complications traditionally associated with filtering surgery were reported. Further research on this stent in a larger group of patients is needed to assess its role in glaucoma therapy.

Use of spaceflight and spaceflight simulation to evaluate osteoprotegerin for treatment of disuse osteoporosis

International Nuclear Information System (INIS)

Bateman, Ted A.; Stodieck, Louis S.; Ferguson, Virginia L.; Simske, Steven J.; Kostenuik, Paul J.

2000-01-01

Osteoprotegerin (OPG) is a recently discovered naturally circulating protein (Amgen Inc.) that plays a role in regulating bone density. It inhibits the ability of osteoclasts to resorb bone by blocking the action of OPG ligand (OPGL). This limits osteoclastogenesis and the activation of mature osteoclasts and induces osteoclast apoptosis. Transgenic mice, altered to over-express OPG, develop increased bone density via dual X-ray absorptiometry analysis, similar to that of osteopetrotic (op/op) mice. Recombinant injection of OPG in mice increases metaphyseal trabecular bone volume of both the proximal tibia and distal femur. Recombinant OPG also ameliorates the effects of estrogen loss in ovariectomized (OVX) rats, causing an increase in bone volume and decreased osteoclast numbers relative to placebo controls. OPG has been examined for its ability to treat both tail suspension and nerve crush. OPG returns the mechanical properties of tail suspended mice to the levels of placebo treated nonsuspended controls. This increase in mechanical properties is not caused by returning formation levels to normal, but rather by inhibiting resorption while increasing percent mineral composition. OPG is also efficacious in treating nerve crush induced osteoporosis. The differences in bone mass (a consequence of disuse) between the crushed limb and contralateral control (noncrushed) is decreased by OPG treatment

Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

International Nuclear Information System (INIS)

Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

2010-01-01

Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

Science.gov (United States)

Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

2013-01-01

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice.

Science.gov (United States)

Trezise, A E; Ratcliff, R; Hawkins, T E; Evans, M J; Freeman, T C; Romano, P R; Higgins, C F; Colledge, W H

1997-04-01

The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode structurally similar proteins which are members of the ABC transporter superfamily. These genes exhibit complementary patterns of expression in vivo, suggesting that the regulation of their expression may be co-ordinated. We have tested this hypothesis in vivo by examining Cftr and Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)). Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced in the intestine, as compared with littermate wild-type mice. All other Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA expression in the intestines of neonatal and 3- to 4-week-old Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In 10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting that the changes in Mdr1 mRNA levels observed in the Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression and/or function. These data provide further evidence supporting the hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in vivo, and that this co-ordinate regulation is influenced by temporal factors.

Adeno-associated virus LPL(S447X) gene therapy in LDL receptor knockout mice

NARCIS (Netherlands)

Rip, Jaap; Sierts, Jeroen A.; Vaessen, Stefan F. C.; Kastelein, John J. P.; Twisk, Jaap; Kuivenhoven, Jan Albert

2007-01-01

BACKGROUND: Overexpression of lipoprotein lipase (LPL) protects against atherosclerosis in genetically engineered mice. We tested whether a gene therapy vector that delivers human (h) LPL(S447X) cDNA to skeletal muscle could induce similar effects. METHODS: LDL receptor knockout (LDLr-/-) mice were

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

Science.gov (United States)

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging

Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

Science.gov (United States)

Kitamura, Shigeyuki; Sugihara, Kazumi

2014-01-01

1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

Age-related retinopathy in NRF2-deficient mice.

Directory of Open Access Journals (Sweden)

Zhenyang Zhao

2011-04-01

Full Text Available Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms.Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice.Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

Science.gov (United States)

Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

2015-08-15

This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Johansen, J; Marker, O

1996-01-01

To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...... this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient...... and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control....

An adaptation model for trabecular bone at different mechanical levels

Directory of Open Access Journals (Sweden)

Lv Linwei

2010-07-01

Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

Electric shocks are ineffective in treatment of lethal effects of rattlesnake envenomation in mice.

Science.gov (United States)

Johnson, E K; Kardong, K V; Mackessy, S P

1987-01-01

Electrical shocks, even crudely delivered from 'stun guns' and gasoline engine spark plugs, have been reported to be effective in the treatment of snake bite. We thus applied similar electric shocks to mice artificially injected with reconstituted rattlesnake venom at various LD50 multiples. Those envenomated mice treated with electric shock survived no better than the controls. We thus found no evidence that electric shocks crudely administered had any life saving effect in mice.

Lepidium meyenii (Maca increases litter size in normal adult female mice

Directory of Open Access Journals (Sweden)

Gasco Manuel

2005-05-01

Full Text Available Abstract Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i Reproductive indexes group, ii Implantation sites group and iii Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to

Prospective Evaluation of Two iStent® Trabecular Stents, One iStent Supra® Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes.

Science.gov (United States)

Myers, Jonathan S; Masood, Imran; Hornbeak, Dana M; Belda, Jose I; Auffarth, Gerd; Jünemann, Anselm; Giamporcaro, Jane Ellen; Martinez-de-la-Casa, Jose M; Ahmed, Iqbal Ike K; Voskanyan, Lilit; Katz, L Jay

2018-03-01

This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG). Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1-3 glaucoma medications. Subjects received two iStent ® trabecular micro-bypass stents, one iStent Supra ® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations. Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. IOP control was achieved safely with two

Spatial encoding in spinal sensorimotor circuits differs in different wild type mice strains

Directory of Open Access Journals (Sweden)

Schouenborg Jens

2008-05-01

Full Text Available Abstract Background Previous studies in the rat have shown that the spatial organisation of the receptive fields of nociceptive withdrawal reflex (NWR system are functionally adapted through experience dependent mechanisms, termed somatosensory imprinting, during postnatal development. Here we wanted to clarify 1 if mice exhibit a similar spatial encoding of sensory input to NWR as previously found in the rat and 2 if mice strains with a poor learning capacity in various behavioural tests, associated with deficient long term potention, also exhibit poor adaptation of NWR. The organisation of the NWR system in two adult wild type mouse strains with normal long term potentiation (LTP in hippocampus and two adult wild type mouse strains exhibiting deficiencies in corresponding LTP were used and compared to previous results in the rat. Receptive fields of reflexes in single hindlimb muscles were mapped with CO2 laser heat pulses. Results While the spatial organisation of the nociceptive receptive fields in mice with normal LTP were very similar to those in rats, the LTP impaired strains exhibited receptive fields of NWRs with aberrant sensitivity distributions. However, no difference was found in NWR thresholds or onset C-fibre latencies suggesting that the mechanisms determining general reflex sensitivity and somatosensory imprinting are different. Conclusion Our results thus confirm that sensory encoding in mice and rat NWR is similar, provided that mice strains with a good learning capability are studied and raise the possibility that LTP like mechanisms are involved in somatosensory imprinting.

Immunological aspects of Giardia muris and Spironucleus muris infections in inbred and outbred strains of laboratory mice: a comparative study.

Science.gov (United States)

Brett, S J; Cox, F E

1982-08-01

The intestinal flagellates, Giardia muris and Spironucleus muris, cause similar infections in CBA mice as determined by trophozoite and cyst counts. Both parasites occur all along the small intestine with G. muris, being mainly present in the anterior part and S. muris towards the posterior. The early stages of infection are similar in all strains of mice examined and peak levels of both trophozoites and cysts occur 1-2 weeks after infection. All strains of mice overcome the infection but the rate of recovery varies considerably between strains, being most rapid in BALB/c and slowest in A and C57BL.B10. Outbred mice are more variable in their recovery than inbred mice. After recovery, mice are partially resistant to reinfection with the homologous but not the heterologous parasite. Resistance to reinfection with S. muris is greatest in those strains that eliminate the primary infection most rapidly. Giardia muris and S. muris cause similar changes in the mucosa of the small intestine of BALB/c mice with increased intra-epithelial lymphocyte counts from 3 weeks onwards corresponding with the start of the elimination of the parasites from the gut. A reduction in villus height and increase in crypt depth is also characteristic of these infections.

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

DEFF Research Database (Denmark)

Bengtson, Stefan; Knudsen, Kristina Bram; Kyjovska, Zdenka O.

2017-01-01

assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

Stevia and Saccharin Preferences in Rats and Mice

Science.gov (United States)

Bahrani, Mahsa; Zukerman, Steven; Ackroff, Karen

2010-01-01

Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague–Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate). PMID:20413452

Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ-free mice.

Science.gov (United States)

Nascimento, Bruna B; Cartelle, Christiane T; Noviello, Maria de L; Pinheiro, Breno V; de Almeida Vitor, Ricardo W; Souza, Danielle da G; de Vasconcelos Generoso, Simone; Cardoso, Valbert N; Martins, Flaviano Dos S; Nicoli, Jacques R; Arantes, Rosa M E

2017-08-01

Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations

Directory of Open Access Journals (Sweden)

Timothy J. Bauler

2011-03-01

SHP-2 (encoded by PTPN11 is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor kappa B ligand (RANKL was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.

Direct estimation of human trabecular bone stiffness using cone beam computed tomography.

Science.gov (United States)

Klintström, Eva; Klintström, Benjamin; Pahr, Dieter; Brismar, Torkel B; Smedby, Örjan; Moreno, Rodrigo

2018-04-10

The aim of this study was to evaluate the possibility of estimating the biomechanical properties of trabecular bone through finite element simulations by using dental cone beam computed tomography data. Fourteen human radius specimens were scanned in 3 cone beam computed tomography devices: 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan), NewTom 5 G (QR Verona, Verona, Italy), and Verity (Planmed, Helsinki, Finland). The imaging data were segmented by using 2 different methods. Stiffness (Young modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations by using micro-CT were regarded as the reference standard. The 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan) showed good performance in estimating stiffness and shear moduli but was sensitive to the choice of segmentation method. NewTom 5 G (QR Verona, Verona, Italy) and Verity (Planmed, Helsinki, Finland) yielded good correlations, but they were not as strong as Accuitomo 80 (J. Morita MFG., Kyoto, Japan). The cone beam computed tomography devices overestimated both stiffness and shear compared with the micro-CT estimations. Finite element-based calculations of biomechanics from cone beam computed tomography data are feasible, with strong correlations for the Accuitomo 80 scanner (J. Morita MFG., Kyoto, Japan) combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties. Copyright © 2018 Elsevier Inc. All rights reserved.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

Energy Technology Data Exchange (ETDEWEB)

Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

Science.gov (United States)

Deboer, Mark D; Li, Yongli

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

Energy Technology Data Exchange (ETDEWEB)

Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.

2012-10-24

High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

INFLUENCE OF MICROBIOTA IN EXPERIMENTAL CUTANEOUS LEISHMANIASIS IN SWISS MICE

Directory of Open Access Journals (Sweden)

OLIVEIRA Marcia Rosa de

1999-01-01

Full Text Available Infection of Swiss/NIH mice with Leishmania major was compared with infection in isogenic resistant C57BL/6 and susceptible BALB/c mice. Swiss/NIH mice showed self-controlled lesions in the injected foot pad. The production of high levels of interferon-g (IFN-g and low levels of interleukin-4 (IL-4 by cells from these animals suggests that they mount a Th1-type immune response. The importance of the indigenous microbiota on the development of murine leishmaniasis was investigated by infecting germfree Swiss/NIH in the hind footpad with L. major and conventionalizing after 3 weeks of infection. Lesions from conventionalized Swiss/NIH mice were significantly larger than conventional mice. Histopathological analysis of lesions from conventionalized animals showed abscesses of variable shapes and sizes and high numbers of parasitized macrophages. In the lesions from conventional mice, besides the absence of abscess formation, parasites were rarely observed. On the other hand, cells from conventional and conventionalized mice produced similar Th1-type response characterized by high levels of IFN-g and low levels of IL-4. In this study, we demonstrated that Swiss/NIH mice are resistant to L. major infection and that the absence of the normal microbiota at the beginning of infection significantly influenced the lesion size and the inflammatory response at the site of infection.

Respiratory and intraperitoneal infection of mice with encephalomyocarditis cirus

International Nuclear Information System (INIS)

Bogaerts, W.J.C.; Durville-van der Oord, B.J.

1975-01-01

The relationships governing host resistance to viraliinfection were evaluated in mice following respiratory or peritoneal infection with three strains of encephalomyocarditis virus, which were antigenically similar but differed in virulence. The contribution of non-specific resistance to the overall defense of the host was assessed in mice that had received 450 R of X-radiation prior to viral infection. Survival time correlated with the degree of attenuation of the virus strains and was not influenced by sublethal X-irradiation and route of inoculation, provided that the viral dose was expressed in LD 50 units

PGC-1alpha mediates exercise-induced skeletal muscle VEGF expression in mice

DEFF Research Database (Denmark)

Leick, Lotte; Hellsten, Ylva; Fentz, Joachim

2009-01-01

The aim of the present study was to test the hypothesis that PGC-1alpha is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1alpha-dependent mechanism. Whole body PGC-1alpha knockout (KO......) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1alpha KO mice, VEGF protein...... expression was approximately 60-80% lower and the capillary-to-fiber ratio approximately 20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1alpha KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased...

[Premature immunosenescence in catecholamines syntesis deficient mice. Effect of social environment].

Science.gov (United States)

Garrido, Antonio; Cruces, Julia; Iriarte, Idoia; Hernández-Sánchez, Catalina; de Pablo, Flora; de la Fuente, Mónica

Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. To determine if an haploinsufficiency of tyrosine hydroxylase (TH), the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Adult (9±1 months) male ICR-CD1 mice with deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT>50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. TH-HZ>50% mice showed a deteriorated function and redox state in leukocytes respect to WT>50% and similar to old mice. However, TH-HZ<50% animals had similar values to those found in WT<50% mice. The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Detection of toxoplasma gondii antigens in sera from experimentally infected mice

International Nuclear Information System (INIS)

Shojaee, S.; Keshavarz, H.; Rezaian, M.; Mohebali, M.

2007-01-01

Detection of Toxoplasma antigen in serum of mice by Immunoblotting. strain. IgG isolated from rabbits that were immunized with T. gondii Immunoblotting was performed to detect T. gondii antigens in sera of mice. Serum samples from mice experimentally infected with T. gondii RH strain. The value of Immunoblotting in diagnosis of toxoplasmosis in acute stage of infection. The antigen bands detected in serum sample of mice were experimentally infected with T. gondii tachyzoite in immunoblotting. Six bands demonstrated on seventh post infection day six bands were identified. Similarly on sixth day four bands, on day five three bands and on fourth post infection day two bands were identified. No band was detected in control group sera. Immunoblotting is a sensitive method for diagnosis of acute stage of toxoplasmosis. (author)

Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits

International Nuclear Information System (INIS)

Castaneda, S; Largo, R.; Marcos, M.E.; Herrero-Beaumont, G.; Calvo, E.; Rodriguez-Salvanes, F.; Diaz-Curiel, M.

2006-01-01

Experimental models of osteoporosis in rabbits are useful to investigate anabolic agents because this animal has a fast bone turnover with predominant remodelling over the modelling processes. For that purpose, it is necessary to characterize the densitometric values of each type of bony tissue. To determine areal bone mass measurement in the spine and in trabecular, cortical and subchondral bone of the knee in healthy and osteoporotic rabbits. Bone mineral content and bone mineral density were measured in lumbar spine, global knee, and subchondral and cortical bone of the knee with dual energy X-ray absorptiometry using a Hologic QDR-1000/W densitometer in 29 skeletally mature female healthy New Zealand rabbits. Ten rabbits underwent triplicate scans for evaluation of the effect of repositioning. Osteoporosis was experimentally induced in 15 rabbits by bilateral ovariectomy and postoperative corticosteroid treatment for 4 weeks. Identical dual energy X-ray absorptiometry (DXA) studies were performed thereafter. Mean values of bone mineral content at the lumbar spine, global knee, subchondral bone and cortical tibial metaphysis were: 1934±217 mg, 878±83 mg, 149±14 mg and 29±7.0 mg, respectively. The mean values of bone mineral density at the same regions were: 298±24 mg/cm 2 , 455±32 mg/cm 2 , 617±60 mg/cm 2 and 678±163 mg/cm 2 , respectively. (orig.)

Generation of mice with a conditional Foxp2 null allele

OpenAIRE

French, C.; Groszer, M.; Preece, C.; Coupe, A.; Rajewsky, K.; Fisher, S.

2007-01-01

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12?14 of Foxp2; these exons encode the DNA-bindi...

Bone sarcoma induction by radium 224 in C57BL/Do mice

International Nuclear Information System (INIS)

Mays, C.W.; Lloyd, R.D.; Taylor, G.N.; Jones, C.W.

1989-01-01

Ninety-five C57BL/Do mice received radium 224 in ten weekly intraperitoneal injections. Doses ranged from 0.5 to 11.6 Gy. Twelve mice developed bone sarcoma. The risk coefficient ±SD was 2.8 ± 0.8%/Gy and the toxicity of shortlived radium 224 relative to longlived radium 226 was 5.4 ± 2.0. Concurrently, a single injection of 33 kBq/kg plutonium 239 was given to 47 similar mice which had a bone sarcoma risk coefficient of 8.4 ± 0.8%/Gy and toxicity relative to longlived radium 226 of 16 ± 4. Based on the studies of Mueller et al that established the increase in effectiveness with increased protraction of radium 224 dose, it is possible, if the radium 224 total dose had been spread continually over about 1 year, that the toxicity of the radium 224 might have been similar to that of plutonium 239. (author)

Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain

Directory of Open Access Journals (Sweden)

Ellen R. T. Watkiss

2013-01-01

Full Text Available Respiratory syncytial virus (RSV is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM.

Trabecular bone score as a skeletal fragility index in acromegaly patients.

Science.gov (United States)

Hong, A R; Kim, J H; Kim, S W; Kim, S Y; Shin, C S

2016-03-01

Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients. Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients. We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis. Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041). Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.

Pavlovian conditioning of multiple opioid-like responses in mice.