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Sample records for bone histomorphometry osteocalcin

  1. Osteocalcin: an emerging biomarker for bone turnover

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    Brijesh Rathore

    2016-09-01

    Full Text Available Osteocalcin (OC is produced by osteoblasts during bone formation. OC is excreted into urine by glomerular filtration and can be found as fragments in urine. The presence of three vitamin K-dependent and #947;-carboxyglutamic acid residues is critical for osteocalcin's structure, which appears to regulate the maturation of bone mineral. Recent bone biology research have highlighted the importance of bone not only as a structural scaffold to support the human body, but also as a regulator of a metabolic processes that are independent of mineral metabolism. Circulating osteocalcin is present either as carboxylated or as undercarboxylated forms. Increased serum level of osteocalcin is linked with increased bone mineral density. The importance of the bone and ndash;kidney relation in physiologic regulation of mineral ion has also been extensively studied and documented. Several workers have uncovered the role of insulin as an additional factor involved in the skeletal remodelling process. Evidences are available which shows that osteoblastic insulin signalling is important for glucose metabolism. The measurement of OC in urine samples could be used as an index of bone turnover in monitoring bone metabolism. In this review, we have tried to explain different roles of OC, however further studies are required to elucidate the metabolic and hormonal role of OC in human body. [Int J Res Med Sci 2016; 4(9.000: 3670-3674

  2. Predicting vertebral bone strength by vertebral static histomorphometry

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    The study investigates the relationship between static histomorphometry and bone strength of human lumbar vertebral bone. The ability of vertebral histomorphometry to predict vertebral bone strength was compared with that of vertebral densitometry, and also with histomorphometry and bone strength...... of the entire vertebral bodies (L-2) were used for histomorphometry. The other iliac crest biopsies and the L-3 were destructively tested by compression. High correlation was found between BV/TV or Tb.Sp and vertebral bone strength (absolute value of r = 0.86 in both cases). Addition of Tb.Th significantly...... of improving the prediction of bone strength of the vertebral body. The correlations between BV/TV of L-2 and bone strength of L-3 were comparable with the correlation obtained by quantitative computed tomography (QCT), peripheral QCT (pQCT), and dual-energy X-ray absorptrometry (DEXA) of L-3 and bone strength...

  3. Histologic diagnosis of metabolic bone diseases: bone histomorphometry

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    L. Dalle Carbonare

    2011-09-01

    Full Text Available Histomorphometry or quantitative histology is the analysis on histologic sections of bone resorption parameters, formation and structure. It is the only technique that allows a dynamic evaluation of the activity of bone modelling after labelling with tetracycline. Moreover, the new measurement procedures through the use of the computer allow an assessment of bone microarchitecture too. Histomorphometric bone biopsy is a reliable and well-tolerated procedure. Complications are reported only in 1% of the subjects (hematoma, pain, transient neuralgia. Histomorphometry is used to exclude or confirm the diagnosis of osteomalacia. It is employed in the evaluation of bone damage associated with particular treatments (for example, anticonvulsants or in case of rare bone diseases (osteogenesis imperfecta, systemic mastocytosis. It is also an essential approach when clinical, biochemical and other diagnostic data are not consistent. Finally, it is a useful method to understand the pathophysiologic mechanisms of drugs. The bone sample is taken at the level of iliac crest under local anesthesia. It is then put into methyl-metacrilate resin where the sections are prepared for the microscopic analysis of the various histomorphometric parameters.

  4. Serum osteocalcin and bone mineral density in postmenopausal women

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    Lie T. Merijanti Susanto

    2016-02-01

    Full Text Available Since high bone turnover is associated with decreased bone mass, biochemical markers of bone remodeling, such as serum osteocalcin, may be used to assess osteoporosis and to predict fractures in elderly women, particulary those involving trabecular bone, and use of a combination of bone mineral density (BMD and biochemical markers may improve fracture prediction. The serum levels of osteocalcin constitute a specific biochemical parameter of bone formation. Compared to imaging techniques, assays for osteocalcin are safe, noninvasive and easily performed. The aim of this study was to determine the relationship of serum osteocalcin and BMD in postmenopausal women. A cross sectional study was performed on 53 postmenopausal women in South Jakarta from February to April 2010. The subjects were assessed for anthropometric characteristics, serum osteocalcin levels and BMD. BMD was measured at the lumbar spine, right femoral neck and at the left distal radius by dual energy X-ray absorptiometry (DXA. Mean serum osteocalcin was 28.99 ± 10.02 ng/ml. The Pearson correlation test on all subjects indicated a significant inverse correlation between serum osteocalcin and femoral neck BMD (r = - 0.29; p=0.034. By arranging the data into tertiles, a significant association was found in non-obese subjects between mean femoral neck BMD and serum osteocalcin (p=0.036. The Tukey posthoc multiple comparison test showed a significant mean difference in femoral neck BMD between the lowest and the highest tertiles of osteocalcin serum concentrations (p=0.028. Maintenance of body weight is important for maintaining BMD in postmenopausal women.

  5. Histomorphometry of Trabecular Bone of Caudal Vertebrae During Rat Pregnancy

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    S.M. Shahtaheri

    2003-04-01

    Full Text Available Pregnancy make demands upon maternal calcium hemeostasis and the extent to which the maternal bone mass is effected remains uncertain. Recently changes in the bone mass during human pregnancy have been associated also with the transformation of the cancellous architecture and the bone surface available for exchange. These jistomorphometrical structural changes were examined further in an animal model. Using uniparous laboratory rats fed at libitum, the histomorphometry of cancellous bone was compared in undecalcified of caudal vertebrae. Between 3 and 6 sections (8 m were analysed by an automated trabecular analysis system (TAS which measures a comprehensive range of structural variables including the trabecular separation, number, connectivity and width. There was an early stimulation of bone formation that was indicated by generation of thicker and interconnected trabeculae. However in caudal vertebrae, there were architectural changes in cancellous bone commencing with a significant increase in the trabecular separation. ‌‌ It was concluded that strengthens the cancellous component of the maternal skeleton possibly to counter increased load and to facilitate mineral mobilisation in maternal/neonate exchange during the subsequent lactation period.

  6. Trabecular bone histomorphometry in humans with Type 1 Diabetes Mellitus.

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    Armas, Laura A G; Akhter, Mohammed P; Drincic, Andjela; Recker, Robert R

    2012-01-01

    Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone microarchitecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex-matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 μm resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. [1]. Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility.

  7. Comparison of histomorphometry and 85Sr uptake in induced heterotopic bone in rats

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    Solheim, E; Pinholt, E M; Bang, G;

    1992-01-01

    Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by 85Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of 85Sr uptake were ca...

  8. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

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    Jin Shao

    2015-01-01

    Full Text Available Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG, sclerostin (SOST, and Dickopf (DKK which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN, which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.

  9. The reliability and representativity of non-dynamic bone histomorphometry in uremic osteodystrophy

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    Heaf, J G; Pødenphant, J; Gammelgaard, Bente

    1993-01-01

    In order to evaluate the reliability and representativity of iliac crest bone biopsy in uremic osteodystrophy, non-dynamic bone histomorphometry was performed post-mortem on the right and left iliac crests and the 3rd lumbar vertebra in 20 patients with chronic uremia. High (> 0.8) right-left cor...

  10. Drynaria fortunei J. Sm. improves the bone mass of ovariectomized rats through osteocalcin-involved endochondral ossification.

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    Lee, Yong-Eng; Liu, Hwa-Chang; Lin, Yi-Ling; Liu, Shing-Hwa; Yang, Rong-Sen; Chen, Ruei-Ming

    2014-12-02

    Our previous study showed that Drynaria fortunei J. Sm. (Kunze), a traditional Chinese medical herb, can promote osteoblast differentiation and maturation. This study was further aimed to confirm the traditional effects of Kunze on the bone mass of ovariectomized rats. Female Wistar rats were given an ovariectomy and then administered the water extract of Kunze (WEK). Systemic and tissue toxicities of WEK were assessed. A biomechanical test, bone mineral contents, and bone histomorphometry were analyzed to determine the effects of the WEK on the bone mass. Levels of osteocalcin (OCN) in bone tissues were determined by immunohistochemistry and immunoblotting. The effects of naringin, one of the bioactive compounds of the WEK, on the bone mass were evaluated. A bilateral ovariectomy in rats caused a time-dependent decrease in levels of serum 17β-estradiol. Exposure of ovariectomized rats to the WEK at 0.5 and 1g/kg body weight/day for 1, 2, 3, and 6 months did not induce systemic or tissue toxicities. Biomechanical testing and a bone mineral content analysis showed that the ovariectomy decreased the bone torsion force and bone ash in time-dependent manners. In comparison, after exposure to the WEK, the ovariectomy-induced reductions in the bone torsion force and bone ash were significantly alleviated. In parallel, results of a bone histomorphometric assay further revealed that the ovariectomy caused significant diminution in the production of prehypertrophic chondrocytes and trabecular bone but enhanced hypertrophic chondrocyte numbers in the growth plate. However, exposure to the WEK lowered ovariectomy-induced changes in these cellular events. As to the mechanism, the WEK increased OCN biosynthesis in bone tissues of ovariectomized rats. Administration of naringin to ovariectomized rats caused significant amelioration of the bone strength, bone mineral contents, and trabecular bone amounts. This study shows that the WEK can translationally promote the bone mass in

  11. Osteocalcin/fibronectin-functionalized collagen matrices for bone tissue engineering.

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    Kim, S G; Lee, D S; Lee, S; Jang, J-H

    2015-06-01

    Collagen is the most abundant protein found in the extracellular matrix and is widely used to build scaffolds for biomedical applications which are the result of its biocompatibility and biodegradability. In the present study, we constructed a rhOCN/FNIII9-10 fusion protein and rhOCN/FNIII9-10-functionalized collagen matrices and investigated the potential value for bone tissue engineering. In vitro studies carried out with preosteoblastic MC3T3-E1 cells showed that rhOCN/FNIII9-10 fusion protein promoted cell adhesion and the mRNA levels of osteogenic markers including osteocalcin, runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen type I. In addition, rhOCN/FNIII9-10-functionalized collagen matrices showed significant induction of the ALP activity more than rhFNIII9-10-functionalized collagen matrices or collagen matrices alone. These results suggested that rhOCN/FNIII9-10-functionalized collagen matrices have potential for bone tissue engineering.

  12. Comparison of bone histomorphometry and μCT for evaluating bone quality in tail-suspended rats

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    Sun, Lian-Wen; Huang, Yun-Fei; Wang, Ying; Luan, Hui-Qin; Fan, Yu-Bo

    2014-10-01

    Astronauts often suffer from microgravity-induced osteoporosis due to their time in space. Bone histomorphometry, the 'gold standard' technique for detecting bone quality, is widely used in the evaluation of osteoporosis. This study investigates whether μCT has the same application value as histomorphometry in the evaluation of weightlessness-induced bone loss. A total of 24 SD rats were distributed into three groups (n = 8, each): tail-suspension (TS), TS plus active exercise (TSA), and control (CON). After 21 days, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) and μCT, and microstructure was measured by μCT and histomorphometry. BMD was found to have decreased significantly in TS and TSA compared with the CON group. The results of the μCT measurements showed that a change in BMD mainly occurred in the trabecular bone, and the trabecular BMD increased significantly in the TSA compared with the TS group. The comparison of μCT and histomorphometry showed that TS led to a significant decrease in bone volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N), and it led to an increase in trabecular separation (Tb.Sp). However, active exercise can prevent these changes. Significant differences in most parameters between TSA and CON were found by μCT but not by histomorphometry. Additionally, the parameters of these two methods are highly correlated. Therefore, the application value of μCT is as good as histomorphometry and DXA in the diagnosis of weightlessness-induced osteoporosis and is even better in evaluating the efficacy of exercise.

  13. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

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    Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

    2003-01-01

    The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with t

  14. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism.

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    Ducy, P

    2011-06-01

    Bone remodelling, which maintains bone mass constant during adulthood, is an energy-demanding process. This, together with the observation that the adipocyte-derived hormone leptin is a major inhibitor of bone remodelling, led to the hypothesis that bone cells regulate energy metabolism through an endocrine mechanism. Studies to test this hypothesis identified osteocalcin, a hormone secreted by osteoblasts, as a positive regulator of insulin secretion, insulin resistance and energy expenditure. Remarkably, insulin signalling in osteoblasts is a positive regulator of osteocalcin production and activation via its ability to indirectly enhance bone resorption by osteoclasts. In contrast, leptin is a potent inhibitor of osteocalcin function through its effect on the sympathetic tone. Hence, osteocalcin is part of a complex signalling network between bone and the organs more classically associated with the regulation of energy homeostasis, such as the pancreas and adipose tissue. This review summarises the molecular and cellular bases of the present knowledge on osteocalcin biology and discusses the potential relevance of osteocalcin to human metabolism and pathology.

  15. Diagnosis value of serum ALP and osteocalcin in early prostate cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Zong-Yong Cheng

    2016-01-01

    Objective:To explore the role and significance of the joint detection of serum alkaline phosphatase (ALP) and osteocalcin in prostate cancer bone metastases.Methods:A total of 87 cases of prostate cancer patients were diagnosed by radionuclide bone imaging, and 51 cases of them were included in the bone metastases group, while the other 36 cases were selected as the non-metastases group. Serum levels of ALP and osteocalcin of all patients were detected. The sensitivity, specificity, accuracy, likelihood ratio and the predictive value of patients in the two groups were analyzed. The sensitivity and specificity of the combined detection of ALP and osteocalcin and their expression levels in different bone metastases degrees were analyzed.Results:Serum ALP and osteocalcin levels of patients in metastases group were higher than those in non-metastases group and normal control group. In non-metastases group, the ALP level was higher than that in normal control group, while its osteocalcin level was lower than that in control group (P<0.05); The sensitivities of ALP and osteocalcin were 77.2% and 70.6%, respectively, and their specificities were 61.1% and 54.6%, respectively. The sensitivity and specificity became 93.3% and 82.33% in combined detection of ALP and osteocalcin, which was significantly higher than the single detection (P<0.05). The expression levels of ALP and osteocalcin increased with the increase of the metastases degrees (P<0.05). Conclusions:Combined detection of ALP and osteocalcin can be used in the early diagnosis of prostate cancer with improved diagnostic efficiency.

  16. Open source software for semi-automated histomorphometry of bone resorption and formation parameters.

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    van 't Hof, Rob J; Rose, Lorraine; Bassonga, Euphemie; Daroszewska, Anna

    2017-06-01

    Micro-CT analysis has become the standard method for assessing bone volume and architecture in small animals. However, micro-CT does not allow the assessment of bone turnover parameters such as bone formation rate and osteoclast (OC) number and surface. For these crucial variables histomorphometric analysis is still an essential technique. Histomorphometry however, is time consuming and, especially in mouse bones, OCs can be difficult to detect. The main purpose of this study was to develop and validate a relatively easy and rapid method to measure static and dynamic bone histomorphometry parameters. Here we present the adaptation of established staining protocols and three novel open source image analysis packages: TrapHisto, OsteoidHisto and CalceinHisto that allow rapid, semi-automated analysis of histomorphometric bone resorption, osteoid, and calcein double labelling parameters respectively. These three programs are based on ImageJ, but use a relatively simple user interface that hides the underlying complexity of the image analysis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Effect of strontium ranelate on the bone histomorphometry after weightlessness in rats

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    A-na LAI; Yang, Rui; Zhang, Zhen; Wang, Mei; Chen, Rong-Ping; Zhou, Ying; Huang, Zhen; Hong CHEN

    2011-01-01

    Objective To investigate the effect of strontium ranelate(SR) on the bone histomorphometry of tail-suspended rat.Methods Thirty male SD rats(3 months old) were randomly divided into five groups(6 each): rats in SR-1 group underwent tail suspension for 4 weeks and given SR simultaneously.In SR-2 group rats received tail suspension for 4 weeks and given SR thereafter.In SR-3 group rats underwent tail suspension for 4 weeks and given SR during the whole course.In control-1 group rats underwent t...

  18. Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    . In addition, connectivity density was measured (ConnEulor method). The results showed that the age-related changes in the static histomorphometric measures are generally similar in the iliac crest and the vertebral body, and that these age-related changes are independent of gender. An exception, however...... the generally similar pattern in age-related changes at these two skeletal sites. The highest correlation coefficient was found for trabecular separation (Tb.Sp; r = 0.63). Trabecular bone volume showed a correlation coefficient of r = 0.59. It is concluded that static histomorphometry performed on one skeletal...

  19. Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study.

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    Thomsen, J S; Ebbesen, E N; Mosekilde, Li

    2002-01-01

    We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. Three female subjects (80, 88, and 90 years) had a known vertebral fracture of L-2. The iliac crest biopsies and 9-mm-thick mediolateral slices of half the entire vertebral bodies were embedded in methylmetacrylate, stained with aniline blue, and scanned into a computer with a flatbed image scanner at a high resolution. With a custom-made computer program the following static histomorphometric measures were determined: trabecular bone volume; marrow and bone space star volume; node-strut analysis; trabecular bone pattern factor; trabecular thickness; trabecular number; trabecular separation; and anisotropy of bone and marrow phase. In addition, connectivity density was measured (ConnEulor method). The results showed that the age-related changes in the static histomorphometric measures are generally similar in the iliac crest and the vertebral body, and that these age-related changes are independent of gender. An exception, however, is connectivity density, where the age-related changes are similar for women and men in the vertebral body but significantly different in the iliac crest. Furthermore, the results showed that the histomorphometric measures were weakly intercorrelated between the iliac crest and the vertebral body, despite the generally similar pattern in age-related changes at these two skeletal sites. The highest correlation coefficient was found for trabecular separation (Tb.Sp; r = 0

  20. Effect of strontium ranelate on the bone histomorphometry after weightlessness in rats

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    A-na LAI

    2011-06-01

    Full Text Available Objective To investigate the effect of strontium ranelate(SR on the bone histomorphometry of tail-suspended rat.Methods Thirty male SD rats(3 months old were randomly divided into five groups(6 each: rats in SR-1 group underwent tail suspension for 4 weeks and given SR simultaneously.In SR-2 group rats received tail suspension for 4 weeks and given SR thereafter.In SR-3 group rats underwent tail suspension for 4 weeks and given SR during the whole course.In control-1 group rats underwent tail suspension for 4 weeks and not given SR,and in control-2 group rats did not undergo tail suspension and were not given SR.Animals were sacrificed 8 weeks(including 4 weeks of tail suspension later,and the cancellous bone of upper end of tibia was then analyzed histomorphologically.Results There were no significant differences between control-2 group and the 3 SR groups in static parameters [trabecular bone area(%Tb.Ar,trabecular thickness(Tb.Th,trabecular number(Th.N and trabecular separation(Tb.Sp] and dynamic parameters [labeled perimeter(%L.Pm,bone formation rate(BFR/TV,mineral apposition rate(MAR,and osteoclast number(Oc.N].On then other hand,Tb.Th,Th.N,%Tb.Ar,%L.Pm,BFR/TV and MAR increased,and Tb.Sp and Oc.N decreased in the 3 SR groups compared with those in control-1 group,implying that the bone mass was increased.No significant difference was found in all the parameters mentioned above between the 3 SR groups.Conclusions Strontium ranelate may obviously improve the bone histomorphometry of tail suspended rats,and have an effect on preventing osteoporosis caused by agravity.

  1. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

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    Lambert, Laura J.; Challa, Anil K.; Niu, Aidi; Zhou, Lihua; Tucholski, Janusz; Johnson, Maria S.; Nagy, Tim R.; Eberhardt, Alan W.; Estep, Patrick N.; Kesterson, Robert A.

    2016-01-01

    ABSTRACT Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research. PMID:27483347

  2. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

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    Laura J. Lambert

    2016-10-01

    Full Text Available Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap, is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA, glucose tolerance testing (GTT, insulin tolerance testing (ITT, microcomputed tomography (µCT, and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.

  3. The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

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    Norazlina Mohamed

    2012-01-01

    Full Text Available Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja, a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV, decreased trabecular number (Tb.N, and increased trabecular separation (Tb.Sp. Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N and trabecular separation (Tb.Sp. Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

  4. Comparison of histomorphometry and [sup 85]Sr uptake in induced heterotopic bone in rats

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    Solheim, E.; Pinholt, E.M. (Institute for Surgical Research, Rikshospitalet, University of Oslo (Norway)); Bang, G. (Department of Oral Pathology and Forensic Odontology, University of Bergen (Norway)); Sudmann, E. (Hagavik Orthopedic Hospital, University of Bergen (Norway))

    1992-01-01

    Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by [sup 85]Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of [sup 85]Sr uptake were calculated: the osteogenic index [(counts/min/mg implant)/(counts/min/mg os ilium)] and an index that we have called the osteoquantum index in which the weight of the implant is disregarded [(counts/min implant)/(counts/min/mg os ilium)]. The osteoquantum index showed a linear relationship to the area of the induced bone with a correlation coefficient (r) of 0.90. Only weak linear relationships were found between the osteogenic index and the area of the bone (r = 0.32) and between the osteogenic index and the osteoquantum index (r = 0.33). The osteoquantum index and the area of the induced bone both increased with increasing mass of implanted DBM, whereas the osteogenic index did not change. (au).

  5. The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats.

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    Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

    2012-01-01

    Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

  6. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT and 21 controls (CG. Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01. Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%. The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005, but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

  7. Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Nicola Napoli

    Full Text Available BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D. Moreover, the association between osteocalcin and parameters of β-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve β-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1:1 and followed up for one year. Changes in bone formation (osteoclacin and resorption (beta-CrossLaps markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01 while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and β-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. CONCLUSIONS: Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to β-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction.

  8. Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages.

    Science.gov (United States)

    Arya, Nlin; Moonarmart, Walasinee; Cheewamongkolnimit, Nareerat; Keratikul, Nutcha; Poon-Iam, Sawinee; Routh, Andrew; Bumpenpol, Pitikarn; Angkawanish, Taweepoke

    2015-11-01

    Bone turnover markers could offer a potential alternative means for the early diagnosis of metabolic bone disease in young growing elephants although the baseline of bone turnover markers in elephant is not well established. The aim of this study was to determine any relationship between the age of captive Asian elephants (Elephas maximus) and markers of bone formation. Serum samples from 24 female Asian elephants were collected to evaluate levels of two bone formation markers, namely, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Both intact and N-terminal midfragment OC and BAP were negatively correlated with age. The findings demonstrate that younger elephants have a higher rate of bone turnover than older elephants. Use of these and additional bone markers could lead to the establishment of validated protocols for the monitoring of bone disease in elephants.

  9. Sequence preservation of osteocalcin protein and mitochondrial DNA in bison bones older than 55 ka

    Science.gov (United States)

    Nielsen-Marsh, Christina M.; Ostrom, Peggy H.; Gandhi, Hasand; Shapiro, Beth; Cooper, Alan; Hauschka, Peter V.; Collins, Matthew J.

    2002-12-01

    We report the first complete sequences of the protein osteocalcin from small amounts (20 mg) of two bison bone (Bison priscus) dated to older than 55.6 ka and older than 58.9 ka. Osteocalcin was purified using new gravity columns (never exposed to protein) followed by microbore reversed-phase high-performance liquid chromatography. Sequencing of osteocalcin employed two methods of matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS): peptide mass mapping (PMM) and post-source decay (PSD). The PMM shows that ancient and modern bison osteocalcin have the same mass to charge (m/z) distribution, indicating an identical protein sequence and absence of diagenetic products. This was confirmed by PSD of the m/z 2066 tryptic peptide (residues 1 19); the mass spectra from ancient and modern peptides were identical. The 129 mass unit difference in the molecular ion between cow (Bos taurus) and bison is caused by a single amino-acid substitution between the taxa (Trp in cow is replaced by Gly in bison at residue 5). Bison mitochondrial control region DNA sequences were obtained from the older than 55.6 ka fossil. These results suggest that DNA and protein sequences can be used to directly investigate molecular phylogenies over a considerable time period, the absolute limit of which is yet to be determined.

  10. Development of new criteria for cortical bone histomorphometry in femoral neck: intra- and inter-observer reproducibility.

    Science.gov (United States)

    Tong, Xiao-Yu; Malo, Markus; Tamminen, Inari S; Isaksson, Hanna; Jurvelin, Jukka S; Kröger, Heikki

    2015-01-01

    Histomorphometry is commonly applied to study bone remodeling. Histological definitions of cortical bone boundaries have not been consistent. In this study, new criteria for specific definition of the transitional zone between the cortical and cancellous bone in the femoral neck were developed. The intra- and inter-observer reproducibility of this method was determined by quantitative histomorphometry and areal overlapping analysis. The undecalcified histological sections of femoral neck specimens (n = 6; from men aged 17-59 years) were processed and scanned to acquire histological images of complete bone sections. Specific criteria were applied to define histological boundaries. "Absolute cortex area" consisted of pure cortical bone tissue only, and was defined mainly based on the size of composite canals and their distance to an additional "guide" boundary (so-called "preliminary cortex boundary," the clear demarcation line of density between compact cortex and sparse trabeculae). Endocortical bone area was defined by recognizing characteristic endocortical structures adjacent to the preliminary cortical boundary. The present results suggested moderate to high reproducibility for low-magnification parameters (e.g., cortical bone area). The coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer study and from 0.09 to 16.41 in the inter-observer study. However, the intra-observer reproducibility of some high-magnification parameters (e.g., osteoid perimeter/endocortical perimeter) was lower (CV %, 0.33-87.9). The overlapping of three histological areas in repeated analyses revealed highest intra- and inter-observer reproducibility for the absolute cortex area. This study provides specific criteria for the definition of histological boundaries for femoral neck bone specimens, which may aid more precise cortical bone histomorphometry.

  11. Bone metabolism in advanced cholestatic liver disease : Analysis by bone histomorphometry

    NARCIS (Netherlands)

    Guichelaar, MMJ; Malinchoc, M; Sibonga, J; Clarke, BL; Hay, JE

    2002-01-01

    Despite the clinical importance of cholestatic osteopenia, little is known about its pathophysiologic mechanism. By tetracycline-labeled histomorphometric analysis of bone biopsies taken at the time of liver transplantation, we prospectively evaluated bone resorption and formation in 50 consecutive

  12. How many patients are needed? Variation and design considerations in bone histomorphometry.

    Science.gov (United States)

    Hauge, E M; Mosekilde, L; Melsen, F; Frydenberg, M

    2001-05-01

    In osteoporosis research, bone histomorphometry plays an important role in documenting the biological effects and possible side-effects of new drug treatments. To ensure that the study is properly scaled, it is important to be concerned with the risk of type II error; that is, the risk of failing to detect a real difference. We therefore calculated the necessary sample size in bone histomorphometric studies according to a specified difference of 15% between two groups. The calculations were based on variance components estimated from three different studies: women with a distal fracture of the forearm (n = 22); patients with pituitary insufficiency (n = 21); and patients with primary hyperparathyroidism (n = 21). Using a significance level of 0.05 and a risk of type II error of 0.20, the statistical power of two different designs was compared: a single biopsy design comparing the responses in two groups after the treatment; and a paired biopsy design in which individual differences (posttreatment minus baseline) were calculated before the comparison of the two groups. We found that the mineral apposition rate, wall thickness, and erosion depth are statistically powerful indices that, in the single biopsy design, require no more than n = 25 in each group to detect differences of 15% between the groups. Bone volume, erosion surface, osteoid surface, mineralizing surface, and activation frequency need group sizes of 100-600 individuals to find a 15% difference to be statistically significant. However, the effect of bisphosphonate treatment, for instance, is large enough to reduce the group size to 20 individuals concerning activation frequency. The remodeling balance reaches extreme group sizes of several thousand for a 15% difference to be statistically significant, but for a 5 microm (approximately 150%) improvement, about 100 individuals are required in the single biopsy design. An analysis of the components of variance showed that the variation between individuals

  13. Maintaining Restored Bone with Bisphoshonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone Mass

    Science.gov (United States)

    Jee, W. S. S.; Tang, L.; Ke, H. Z.; Setterberg, R. B.; Kimmel, D. B.

    1993-01-01

    This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an anti-resorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE2/kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE2 treatment and began treatment with 1 or 5 micro-g/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the proximal tibial metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE2 treatment was stopped, the PGE2-induced cancellous bone disappeared. In contrast, 5 micro-g of Risedronate inhibited the bone loss and maintained it at the PGE2 treatment level. The key dynamic histomorphometry value for the restore (R) and maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 micro-g Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5 micro-g Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE2 after discontinuing PGE2 by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.

  14. Maintaining Restored Bone with Bisphosphonate in the Ovariectomized Rat Skeleton: Dynamic Histomorphometry of Changes in Bone Mass

    Science.gov (United States)

    Jee, W. S. S.; Tang, L.; Ke, H. Z.; Setterberg, R. B.; Kimmel, D. B.

    1993-01-01

    This experiment contains the crucial data for the Lose, Restore and Maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses ovariectomy (ox) to lose bone, an anabolic agent to restore bone mass and then switches to an antiresorptive agent to maintain bone mass. We ox'd or sham-ox'd rats for 150 days (Loss Phase), treated them with 6 mg PGE(sub 2)kg/d for 75 days to restore lost cancellous bone mass (Restore Phase) and then stopped PGE(sub 2) treatment and began treatment with 1 or 5 micrograms/kg Risedronate, a bisphosphonate twice a week for 60 days (Maintain Phase). During the Loss Phase, cancellous bone volumes of the Proximal Tibial Metaphysis (PTM) in the ox'd rat fell to 19% of initial controls. During the Restore Phase, the PTM bone volume in ox'd rats doubled. However, when PGE(sub 2) treatment was stopped, the PGE(sub 2)-induced cancellous bone disappeared. In contrast, 5 miligrams of Risedronate inhibited the bone loss and maintained it at the PGE(sub 2) treatment level. The key dynamic histomorphometry value for the Restore (R) and Maintenance (M) phases was the ratio of bone formation to resorption rates. The ratio was elevated to 5.8 in the R phase and depressed to 0.4 for no and 1 miligram Risedronate treated M phase and to a ratio of near unity of 1.1 for the 5miligrams Risedronate treatment. These findings indicate that we were successful in maintaining the new PTM bone induced by PGE(sub 2) after discontinuing PGE(sub 2) by administering enough Risedronate, a resorption inhibitor. We concluded that the LRM concept is correct and such an approach should be considered when employing anabolic agents or growth factors in the treatment of osteoporosis. Continued use of an anabolic agent may not be appropriate because of cost, potential adverse side effects and a loss of efficacy.

  15. Synchrotron radiation X-ray microtomography and histomorphometry for evaluation of chemotherapy effects in trabecular bone structure

    Science.gov (United States)

    Alessio, R.; Nogueira, L. P.; Almeida, A. P.; Colaço, M. V.; Braz, D.; Andrade, C. B. V.; Salata, C.; Ferreira-Machado, S. C.; de Almeida, C. E.; Tromba, G.; Barroso, R. C.

    2014-04-01

    Three-dimensional microtomography has the potential to examine complete bones of small laboratory animals with very high resolution in a non-invasive way. One of the side effects caused by some chemotherapy drugs is the induction of amenorrhea, temporary or not, in premenopausal women, with a consequent decrease in estrogen production, which can lead to bone changes. In the present work, the femur heads of rats treated with chemotherapy drugs were evaluated by 3D histomorphometry using synchrotron radiation microcomputed tomography. Control animals were also evaluated for comparison. The 3D tomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. Results showed significant differences in morphometric parameters measured from the 3D images of femur heads of rats in both analyzed groups.

  16. [The possibility of the serum concentration of osteocalcin determination in lung cancer patients with suspected bone metastases].

    Science.gov (United States)

    Weissensteiner, J; Babušíková, E

    2015-01-01

    The aim of this study was to compare serum levels of biochemical markers of bone metabolism - osteocalcin (OC) in correlation with bone metastases found during whole-body bone scintigraphy in patients with lung cancer. The serum levels of OC as a bone formation marker were determined in 60 patients (46 male, 14 female, mean age 66.65, range 50-84 years) with lung cancer (51 non-small-cell lung cancers - NSCLC and nine small-cell lung cancers - SCLC) and correlated with the presence of bone metastases detected by whole-body bone scintigraphy (hybrid system SPECT/CT: BrightView XCT, Philips Healthcare). Whole-body bone scintigraphy results were compared with OC for each patient with lung cancer and for person from control group of 10 persons (two males, eight females, mean age 52.3, range 34-67 years) with-out malignant disease. By whole-body bone scintigraphy, bone metastases were found in 15 cases (25%), probably in 11 cases (18.33%) and 34 patients (56.67%) were without bone metastases out of 60 patients with lung cancer. The serum levels of OC were above reference range in five cases (8.33%) only with NSCLC and below reference range in 12 cases (20%) - in 10 cases in patients with NSCLC and in two cases in patients with SCLC. In control group of 10 persons, serum level of OC was below reference range only in one case. The serum concentrations of osteocalcin were not correlated with findings performed bywhole-body bone scintigraphy in patients with lung cancer. Osteocalcin serum levels determination probably does not have diagnostic importance in lung cancer patients with suspected bone metastases.

  17. Effects of pioglitazone and fenofibrate co-administration on bone biomechanics and histomorphometry in ovariectomized rats.

    Science.gov (United States)

    Smith, Susan Y; Samadfam, Rana; Chouinard, Luc; Awori, Malaika; Bénardeau, Agnes; Bauss, Frieder; Guldberg, Robert E; Sebokova, Elena; Wright, Matthew B

    2015-11-01

    Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats. An additional group of rats received a combination of pioglitazone + fenofibrate to mimic the effects of a dual PPAR-α/γ agonist. The study consisted of a 13-week treatment phase followed by a 6-week treatment-free recovery period. Pioglitazone significantly reduced biomechanical strength at the lumbar spine and femoral neck compared with rats administered fenofibrate. Co-treatment with pioglitazone + fenofibrate had no significant effect on bone strength in comparison with OVX vehicle controls. Histomorphometric analysis of the proximal tibia revealed that pioglitazone suppressed bone formation and increased bone resorption at both cancellous and cortical bone sites relative to OVX vehicle controls. In contrast, fenofibrate did not affect bone resorption and only slightly suppressed bone formation. Discontinuation of pioglitazone treatment, both in the monotherapy and in the combination therapy arms, resulted in restoration of bone formation and resorption rates, demonstrating reversibility of effects. The above data support the concept that dual activation of PPAR-γ and PPAR-α attenuates the negative effects of PPAR-γ agonism on bone strength.

  18. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  19. The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency.

    Science.gov (United States)

    Chin, Kok-Yong; Abdul-Majeed, Saif; Mohamed, Norazlina; Ima-Nirwana, Soelaiman

    2017-02-15

    Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.

  20. Ovariectomy-induced changes in aged beagles : histomorphometry of rib cortical bone.

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, A. K.; Bhattacharyya, M. H.; Miller, S.; Sacco-Gibson, N.; Center for Mechanistic Biology and Biotechnology; Univ. of Utah; Procter & Gamble Pharmaceuticals

    1998-03-01

    Bone loss associated with estrogen depletion is well documented in cancellous bone but less well characterized in cortical bone. The effects of ovariectomy on the aged beagle skeleton were studied by histomorphometric analysis of the cortical bone in sequential rib biopsies. Biopsies were taken from each ovariectomized or sham-operated dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Just prior to each postoperative biopsy, tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) to provide markers of bone formation. Analysis of sequential rib biopsies provided a means to follow the ovariectomy response over time and to compare each animal against its own baseline. Though ovariectomy did not influence histomorphometric indices at 1 month after surgery, a transient increase in cortical bone formation occurred thereafter, with a sixfold increase over that of sham-operated dogs at 4 months (P < 0.001) and a return to near control levels at 8.5 months. Cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. These data demonstrate for the first time that rib cortical bone is a responsive site for the effects of ovariectomy in aged female dogs.

  1. Osteoblast function and bone histomorphometry in a murine model of Rett syndrome.

    Science.gov (United States)

    Blue, Mary E; Boskey, Adele L; Doty, Stephen B; Fedarko, Neal S; Hossain, Mir Ahamed; Shapiro, Jay R

    2015-07-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2. Approximately 50% of affected females have decreased bone mass. We studied osteoblast function using a murine model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared to wild type (WT) mice. Micro-CT of tibia from 5 week-old Mecp2-null mice showed significant alterations in trabecular bone including reductions in bone volume fraction (-29%), number (-19%), thickness (-9%) and connectivity density (-32%), and increases in trabecular separation (+28%) compared to WT. We also found significant reductions in cortical bone thickness (-18%) and in polar moment of inertia (-45%). In contrast, cortical and trabecular bone from 8 week-old WT and HET female mice were not significantly different. However, mineral apposition rate, mineralizing surface and bone formation rate/bone surface were each decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric analysis of femurs showed decreased numbers of osteoblasts but similar numbers of osteoclasts compared to WT, altered osteoblast morphology and decreased tissue synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts cultured from Mecp2-null mice, which unlike WT osteoblasts did not express MeCP2, had increased growth rates, but reductions in mRNA expression of type I collagen, Runx2 and Osterix compared to WT osteoblasts. These results indicate that MeCP2 deficiency leads to altered bone growth. Osteoblast dysfunction was more marked in Mecp2-null male than in HET female mice, suggesting that expression of MeCP2 plays a critical role in bone development.

  2. 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

  3. Great increase in bone 66 kDa protein and osteocalcin at later stages with healing rat fractures: effect of zinc treatment.

    Science.gov (United States)

    Igarashi, Aki; Yamaguchi, Masayoshi

    2003-02-01

    Fracture healing has been demonstrated to increase production of bone growth factors, and this elevation has been shown to be enhanced by zinc treatment. Moreover, the effect of zinc treatment on production of bone osteocalcin, which is a kind of Ca2+-binding protein localized in bone matrix, at the later stages with bone fracture was investigated. Rats were sacrificed 7 (earlier stage) or 21 (later stage) days after fracture of femoral diaphysis. Femoral-diaphyseal tissues with fracture healing were cultured in a serum-free medium for 24 h. Many proteins in the bone tissues were released into the medium. Bone protein production was markedly elevated 21 days after bone fracture as compared with that of 7 days. A approximately 66 kDa protein molecule, a major protein component which was produced by the diaphyseal tissues during fracture healing, was predominantly increased at the later stages with fracture healing. Bone osteocalcin production was significantly increased during fracture healing. This increase was enhanced at the later stages with fracture healing. The presence of zinc acexamate (10(-4) M) in culture medium caused a significant increase in bone protein and osteocalcin production at 7 or 21 days after bone fracture. The effect of zinc acexamate in increasing bone total protein and osteocalcin production was remarkable at the later stages with fracture healing. Moreover, zinc treatment caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium content in the femoral-diaphyseal tissues of the later stages with fracture healing in vitro. The present study demonstrates that bone protein production is markedly increased at the later stages with fracture healing, and that zinc treatment can enhance production of bone protein components including osteocalcin in vitro. Zinc treatment may stimulate the healing of femoral fracture at earlier and later stages.

  4. The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency

    Science.gov (United States)

    Chin, Kok-Yong; Abdul-Majeed, Saif; Mohamed, Norazlina; Ima-Nirwana, Soelaiman

    2017-01-01

    Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p osteoporosis. PMID:28212283

  5. Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Bortolin, Raul Hernandes; Freire Neto, Francisco Paulo; Arcaro, Carlos Alberto; Bezerra, João Felipe; da Silva, Flávio Santos; Ururahy, Marcela Abbott Galvão; Souza, Karla Simone da Costa; Lima, Valeria Morgiana Gualberto Duarte Moreira; Luchessi, André Ducati; Lima, Francisco Pignataro; Lia Fook, Marcus Vinicius; da Silva, Bartolomeu Jorge; Almeida, Maria das Graças; Abreu, Bento João; de Rezende, Luciana Augusto; de Rezende, Adriana Augusto

    2017-03-01

    Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non-molecular parameters in a chronic animal model of T1DM-induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM-induced bone loss via the effects on the bone formation.

  6. The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2017-02-01

    Full Text Available Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2 gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1 lovastatin 11 mg/kg/day alone; (2 tocotrienol derived from annatto bean (annatto tocotrienol 60 mg/kg/day alone; (3 lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p < 0.05. There was a parallel increase in BMP-2 gene expression in the rats receiving combined treatment (p < 0.05. The combination of annatto tocotrienol and lovastatin exerted either additively or synergistically on selected bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.

  7. Skeletal events of Anastrozole versus Tamoxifen on bone mineral density and bone biomarker osteocalcin in postmenopausal women with early breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lobna R Ezz Elarab; Menha Swellam; Manal M Abdel Wahab; Karima M Maher

    2010-01-01

    Objective:Postmenopausal women with breast cancer are at increased risk of bone loss because of age related estrogen deficiency face which accelerated with the use of aromatase inbibitors (AIs).We aimed to study the effect on bone mineral density (BMD) and bone formation biomarker osteocalcin level in postmenopausal breast cancer patients,for the first three years of adjuvant hormonal treatment of both groups Tamoxifen versus Anastrozol.Methods:One-hundered postmenopausal breast cancers were prospectively randomized to receive either Tamoxifen 20 rag/day (n=50) or Anastrozole 10 mg (n=50).Both BMD and osteocalcin were assessed initially before treatment and then at regular intervals for both groups.Results:Use of Tamoxifen was associated with significant annual decrease in osteocalcin (P=0.001),whereas Anastrozole group had gradual increase of the annual levels (P<0.01).BMD decreased significantly in Anastrozole versus Tamoxifen groups (2.6% vs.0.4%,P<0.001).Osteoporosis T<-2.5 was reported significantly higher in Anastrozole group (P<0.01).Women with initial osteopenia in Anastrozole group showed significant decrease in BMD (P<0.05).The addition of bisphosphonate for patients with early osteoporosis markedly improved both osteocalcin level and BMD.Conclusion:Tamoxifen preserves BMD in postmenopausal breast cancer patients,whereas Anastrozole accelerates age associated fall in BMD especially in the first year of therapy,moreover,the addition of bisphosphonate can help to decrease the skeletal related events associated with treatment to ensure better quality of life with treatment.

  8. Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome.

    Science.gov (United States)

    Yousfi, M; Lasmoles, F; Lomri, A; Delannoy, P; Marie, P J

    2001-05-01

    The Saethre-Chotzen syndrome is characterized by premature fusion of cranial sutures resulting from mutations in Twist, a basic helix-loop-helix (bHLH) transcription factor. We have identified Twist target genes using human mutant calvaria osteoblastic cells from a child with Saethre-Chotzen syndrome with a Twist mutation that introduces a stop codon upstream of the bHLH domain. We observed that Twist mRNA and protein levels were reduced in mutant cells and that the Twist mutation increased cell growth in mutant osteoblasts compared with control cells. The mutation also caused increased alkaline phosphatase and type I collagen expression independently of cell growth. During in vitro osteogenesis, Twist mutant cells showed increased ability to form alkaline phosphatase-positive bone-like nodular structures associated with increased type I collagen expression. Mutant cells also showed increased collagen synthesis and matrix production when cultured in aggregates, as well as an increased capacity to form a collagenous matrix in vivo when transplanted into nude mice. In contrast, Twist mutant osteoblasts displayed a cell-autonomous reduction of osteocalcin mRNA expression in basal conditions and during osteogenesis. The data show that genetic deletion of Twist causing reduced Twist dosage increases cell growth, collagen expression, and osteogenic capability, but inhibits osteocalcin gene expression. This provides one mechanism that may contribute to the premature cranial ossification induced by deletion of the bHLH Twist domain in Saethre-Chotzen syndrome.

  9. The Relationship Among Between Serum Cytokine, Intact PTH, Osteocalcin and Bone Mineral Density Values in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    M. Yıldız

    2002-06-01

    Full Text Available This study was designed to compare the bone mineral density (BMD in 108 postmenopausal women with laboratory data including osteocalcin, intact parathyroid hormone and serum cytokine values. One hundred eigth postmenopausal women were randomly divided into 3 sub groups according to their BMD and medical treatment. The first group consisting of 18 postmenopausal women had no osteoporosis, mean age and mean duration of postmenopausal period were 52.94± 4.90 and 6.5±4.76 years respectively. The second group consisting of 15 postmenopausal women had osteoporosis and was not treated, mean age and mean duration of postmenopausal period were 53.60±8.84 and 9.73± 6.75 years respectively. The third group consisting of 75 postmenopausal osteoporotic women was under medical treatment, mean age nd mean duration of postmenopausal period were 58.52±8.51 and 13.20±8.41 years respectively. Bone mineral density at femur Ward’s triangle, trochanter and lumbar spine t score values were evaluated by dual X ray absorptiometry (DXA. Serum calcium, phosphorous, C-reactive protein, erythrocyte sedimentation rate, cytokines (interleukin-1, IL-1, interleukin-2, IL-2, interleukin-6, IL-6, interleukin-8, IL-8 and tumor necrosis factor alpha TNF-a, osteocalcin, intact parathyroid hormone were measured. In subjects, no significant correlation was observed between BMD t scores of lumbar spine, trochanter, Ward’s triangle and cytokine values. On the other hand, among these groups significant difference was found between age, treatment duration, t scores of lumbar spine, trochanter, Ward’s triangle and postmenopausal period, but not between IL-1, IL-2, IL-6, IL-8, TNF-a, osteocalcin, intact parathyroid. As a conclusion we think BMD (especially in the early postmenopausal period might be correlating with the levels of cytokines in bone microenvironment rather than serum levels. In the early postmenopausal osteoporosis period serum IL-6 value might be supporting to

  10. Immunological detection of osteocalcin in meat and bone meal: a novel heat stable marker for the investigation of illegal feed adulteration.

    Science.gov (United States)

    Kreuz, G; Zagon, J; Broll, H; Bernhardt, C; Linke, B; Lampen, A

    2012-01-01

    A sandwich ELISA was developed for the detection of bovine meat and bone meal (BMBM) in feed, based on polyclonal rabbit antibodies raised against the synthetic N-terminal amino acid sequence 1-9 (YLDHWLGAP) of bovine osteocalcin. To set up a sandwich ELISA pair, a commercial mouse monoclonal capture antibody binding to a highly conserved epitope in the mid-fragment of the peptide was employed. It is shown that the bone marker osteocalcin is immunologically well detectable in BMBM extracts obtained by a simple EDTA-based procedure even in a sample heated up to 145°C. Furthermore, a genus-specific restriction of the major specificity to cattle and horse was possible. The observed bi-specificity is consistent with theoretical predictions. The assay sensitivity with bovine osteocalcin of 1 ng was sufficient to enable the detection of 0.1% BMBM in compound plant feed or fish meal, for which no cross reaction was observed. In general the quantification of osteocalcin in extracts is possible using a standard curve procedure with pure bovine osteocalcin.

  11. The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

    Science.gov (United States)

    Cavolina, J. M.; Evans, G. L.; Harris, S. A.; Zhang, M.; Westerlind, K. C.; Turner, R. T.

    1997-01-01

    A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous

  12. Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study.

    Science.gov (United States)

    Iwamoto, Jun; Seki, Azusa; Sato, Yoshihiro

    2014-07-01

    The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation+vehicle group, an ovariectomy (OVX)+vehicle group, an OVX+minodronic acid (6 μg/kgs.c., every 4 weeks) group, an OVX+teriparatide (20 μg/kgs.c., daily) group, and an OVX+minodronic acid+teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Development of an enzyme-linked immunosorbent assay for detection of chicken osteocalcin and its use in evaluation of perch effects on bone remodeling in caged White Leghorns

    Science.gov (United States)

    Osteocalcin (OC) is a sensitive biochemical marker for evaluating bone turnover in mammals. The role of avian OC is less clear because of a need for a chicken assay. Our objectives were to develop an assay using indirect competitive ELISA for detecting chicken serum OC and use the assay to examine t...

  14. Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls

    DEFF Research Database (Denmark)

    O'Connor, Eibhlis; Mølgaard, Christian; Michaelsen, Kim F.

    2007-01-01

    status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11-12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively......Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3-16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum...

  15. 骨形态计量学目前应用专家共识%Expert consensus about the current application of bone histomorphometry

    Institute of Scientific and Technical Information of China (English)

    陈珺; 张豪; 杨国柱; 陆幸研; 金小冬; 卢丽; 李青南

    2014-01-01

    As a quantitative research technique of bone microstructure and bone mass, bone histomorphometry ( BHMT) has been proposed by Harold Frost, an American orthopedic surgeon, in 1960.For better preservation of bone microstructure, undecalcified embedding and fluorescent labeling in vivo are used to make bone tissue samples for BHMT.More than fifty-year application has proved that BHMT is not only the most common and effective method used for the evaluation of bone turnover and bone mineralization, but also the golden standard for the evaluation of bone metabolism and mineralization.There are two common bone histomorphometry methods.One is proposed by Harold Frost and Webster S.S.Jee, a professor from the Department of Radiation Biology, the Medical College of Utah University, and Sun Valley Hard Tissue Workshops ( abbreviated as BHMT nomenclature system).Another method is developed by the American Society for Bone and Mineral Research (ASBMR), based on a set of stereological techniques for bone microarchitecture measurement, which was created by Dr.Parfitt in 1980.Both nomenclature systems have their own parameters and focus, and are widely used.It needs to choose the most appropriate system according to the particular circumstances.In this paper, we discuss the similarities and differences between the two bone histomorphometry methods, and introduce their main application.%1960年,美国骨整形外科医生Harold Frost提出一种定量研究骨微结构和骨量的技术---骨组织形态计量学(BHMT),其采用不脱钙硬包埋法和活体荧光标记法进行骨组织标本制作,更好地保留了骨组织微细结构。50多年来的实践证实BHMT是目前评价骨转换与骨矿化最常用和有效的实验手段,至今仍是骨代谢和矿化评价的金标准。目前国际上有两套常用的标准骨组织形态计量学方法:一是Harold Frost与美国犹他大学医学院放射生物系Webster S.S.Jee教授及Sun Valley Hard

  16. A technique for evaluating bone ingrowth into 3D printed, porous Ti6Al4V implants accurately using X-ray micro-computed tomography and histomorphometry.

    Science.gov (United States)

    Palmquist, Anders; Shah, Furqan A; Emanuelsson, Lena; Omar, Omar; Suska, Felicia

    2017-03-01

    This paper investigates the application of X-ray micro-computed tomography (micro-CT) to accurately evaluate bone formation within 3D printed, porous Ti6Al4V implants manufactured using Electron Beam Melting (EBM), retrieved after six months of healing in sheep femur and tibia. All samples were scanned twice (i.e., before and after resin embedding), using fast, low-resolution scans (Skyscan 1172; Bruker micro-CT, Kontich, Belgium), and were analysed by 2D and 3D morphometry. The main questions posed were: (i) Can low resolution, fast scans provide morphometric data of bone formed inside (and around) metal implants with a complex, open-pore architecture?, (ii) Can micro-CT be used to accurately quantify both the bone area (BA) and bone-implant contact (BIC)?, (iii) What degree of error is introduced in the quantitative data by varying the threshold values?, and (iv) Does resin embedding influence the accuracy of the analysis? To validate the accuracy of micro-CT measurements, each data set was correlated with a corresponding centrally cut histological section. The results show that quantitative histomorphometry corresponds strongly with 3D measurements made by micro-CT, where a high correlation exists between the two techniques for bone area/volume measurements around and inside the porous network. On the contrary, the direct bone-implant contact is challenging to estimate accurately or reproducibly. Large errors may be introduced in micro-CT measurements when segmentation is performed without calibrating the data set against a corresponding histological section. Generally, the bone area measurement is strongly influenced by the lower threshold limit, while the upper threshold limit has little or no effect. Resin embedding does not compromise the accuracy of micro-CT measurements, although there is a change in the contrast distributions and optimisation of the threshold ranges is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Nerve Growth Factor, Brain-derived Neurotrophic Factor and Osteocalcin gene relationship in energy regulation, bone homeostasis and reproductive organs analyzed by mRNA quantitative evaluation and linear correlation analysis

    OpenAIRE

    Claudia Camerino; Elena Conte; Maria Cannone; Roberta Caloiero; Adriano Fonzino; Domenico Tricarico

    2016-01-01

    Nerve Growth Factor (NGF) / Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2 and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. B...

  18. Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

    Science.gov (United States)

    Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito

    2016-05-01

    We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones.

  19. Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

    Science.gov (United States)

    Naves Díaz, M; Rodríguez Rodríguez, A; Fernández Martín, J L; Serrano Arias, M; Menéndez Rodríguez, P; Cannata Andía, J B

    2007-10-01

    The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.

  20. Anti-osteoporotic effects of Pueraria candollei var. mirifica on bone mineral density and histomorphometry in estrogen-deficient rats.

    Science.gov (United States)

    Suthon, Sarocha; Jaroenporn, Sukanya; Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Malaivijitnond, Suchinda

    2016-04-01

    Although it has been clearly shown that Pueraria mirifica and its phytoestrogens can mimic estrogen in preventing bone loss, as osteoporosis is an asymptomatic disease, the therapeutic effects of P. mirifica should be acknowledged. In this study, 6-month-old female rats were ovariectomized, kept for 4 weeks to induce bone loss, divided into five groups, and treated with P. mirifica at doses of 0, 5, 25, and 50 mg/kg BW/day (PM0, PM5, PM25, and PM50 groups, respectively) or 7 mg/kg BW/day of puerarin (PU group) for 12 weeks. Only the trabecular bone mineral densities (BMDs) of tibia metaphysis (at the 12th, 14th, and 16th week) and total and trabecular BMDs of L4 (at the 16th week) of the PM50 group were significantly higher than those of the PM0 group. However, the BMDs of tibia metaphysis and L4 at the 16th week of the study period were kept significantly lower than those of the 0 week, and the BMD was also significantly lower than that of the 4th week for tibia metaphysis. The trabecular bone area (BV/TV), trabecular number (Tb.N), and osteoblast surface (Ob.S/BS) were significantly higher, and trabecular space (Tb.Sp) was significantly lower in the PM50 group, as compared with those of the PM0 group. This study indicates that P. mirifica could be used as an anti-osteoporotic agent for postmenopausal women. Since P. mirifica could mainly retain bone mass at the levels before bone loss is initiated, the use of other anabolic agents in combination with P. mirifica is recommended for osteoporotic patients.

  1. Functional autonomy, bone mineral density (BMD) and serum osteocalcin levels in older female participants of an aquatic exercise program (AAG).

    Science.gov (United States)

    Pernambuco, Carlos Soares; Borba-Pinheiro, Claudio Joaquim; Vale, Rodrigo Gomes de Souza; Di Masi, Fabrizio; Monteiro, Paola Karynne Pinheiro; Dantas, Estelio H M

    2013-01-01

    The aim of the present study was to evaluate the effects of an AAG on BMD, osteocalcin and functional autonomy in older women. The sample consisted of eighty-two post-menopausal women with low BMD, randomly divided into two groups: the Aquatic Aerobics Group [AAG; n=42; age: 66.8±4.2years], submitted to two weekly sessions over eight months, and the Control Group (GC; n=42; age: 66.9±3.2years), which did not participate in regular exercise. BMD was measured by Dual Energy X-ray Absorptiometry [DXA] of the lumbar and femur, and serum osteocalcin was measured using electrochemiluminescence. A functional autonomy assessment protocol (GDLAM, 2004) was also applied. Statistical analyses used were repeated measures ANOVA and Tukey's post hoc tests. The results showed a significant improvement in tests following the GDLAM protocol: 10 meters walk (10mw) -p=0.003; rising from a ventral decubitus position (RVDP) - Δ%=0.78, paquatic aerobic exercise program can improve functional autonomy and osteocalcin levels, although training did not improve lumbar and total femur BMD in the older women.

  2. Osteocalcin as a hormone regulating glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The number of patients with osteoporosis and diabetesis rapidly increasing all over the world. Bone is recentlyrecognized as an endocrine organ. Accumulatingevidence has shown that osteocalcin, which is specificallyexpressed in osteoblasts and secreted into the circulation,regulates glucose homeostasis by stimulating insulinexpression in pancreas and adiponectin expression inadipocytes, resulting in improving glucose intolerance.On the other hand, insulin and adiponectin stimulateosteocalcin expression in osteoblasts, suggesting thatpositive feedforward loops exist among bone, pancreas,and adipose tissue. In addition, recent studies haveshown that osteocalcin enhances insulin sensitivity andthe differentiation in muscle, while secreted factors frommuscle, myokines, regulate bone metabolism. Thesefindings suggest that bone metabolism and glucosemetabolism are associated with each other through theaction of osteocalcin. In this review, I describe the roleof osteocalcin in the interaction among bone, pancreas,brain, adipose tissue, and muscle.

  3. The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

    DEFF Research Database (Denmark)

    Kamby, C; Egsmose, C; Söletormos, G

    1993-01-01

    Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...... bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...... than that of S-BGP, and the result of BGP measurement was associated with neither extent nor number of bone metastases. However, the BGP values were significantly lower in patients who had visceral metastases, and the median duration of survival after recurrence was 13 months for patients with low S...

  4. Nerve Growth Factor, Brain-derived Neurotrophic Factor and Osteocalcin gene relationship in energy regulation, bone homeostasis and reproductive organs analyzed by mRNA quantitative evaluation and linear correlation analysis

    Directory of Open Access Journals (Sweden)

    Claudia Camerino

    2016-10-01

    Full Text Available Nerve Growth Factor (NGF / Brain-derived Neurotrophic Factor (BDNF and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2 and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt and its receptor(Oxtr was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf/p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300%, 100% and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf/p75NTR in BAT is

  5. Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Osteocalcin Gene Relationship in Energy Regulation, Bone Homeostasis and Reproductive Organs Analyzed by mRNA Quantitative Evaluation and Linear Correlation Analysis

    Science.gov (United States)

    Camerino, Claudia; Conte, Elena; Cannone, Maria; Caloiero, Roberta; Fonzino, Adriano; Tricarico, Domenico

    2016-01-01

    Nerve Growth Factor (NGF)/Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF, and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2, and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt) and its receptor(Oxtr) was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf /p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300, 100, and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf, or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf /p75NTR in BAT is consistent

  6. Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Osteocalcin Gene Relationship in Energy Regulation, Bone Homeostasis and Reproductive Organs Analyzed by mRNA Quantitative Evaluation and Linear Correlation Analysis.

    Science.gov (United States)

    Camerino, Claudia; Conte, Elena; Cannone, Maria; Caloiero, Roberta; Fonzino, Adriano; Tricarico, Domenico

    2016-01-01

    Nerve Growth Factor (NGF)/Brain-derived Neurotrophic Factor (BDNF) and osteocalcin share common effects regulating energy, bone mass, reproduction and neuronal functions. To investigate on the gene-relationship between NGF, BDNF, and Osteocalcin we compared by RT-PCR the transcript levels of Ngf, Bdnf and Osteocalcin as well as of their receptors p75NTR/NTRK1, NTRK2, and Gprc6a in brain, bone, white/brown adipose tissue (WAT/BAT) and reproductive organs of 3 months old female and male mice. Brain and bone were used as positive controls for NGF/BDNF and Osteocalcin respectively. The role of oxitocin(Oxt) and its receptor(Oxtr) was also investigated. Ngf expression shows an opposite trend compared to Bdnf. Ngf /p75NTR expression is 50% higher in BAT than brain, in both genders, but lower in bone. In contrast, Bdnf expression in bone is higher than in brain, but low in BAT/WAT. We found Osteocalcin gene expressed in brain in both genders, but Gprc6a expression is low in brain and BAT/WAT. As expected, Gprc6a gene is expressed in bone. Oxt gene was markedly expressed in brain, Oxtr in the ovaries and in fat and bone in both genders. Ngf is highly expressed in reproductive tissues and p75NTR mRNA levels are respectively 300, 100, and 50% higher in testis/ovaries/uterus than in brain. In contrast, BDNF genes are not expressed in reproductive tissues. As expected, Gprc6a is expressed in testis but not in the ovaries/uterus. A significant correlation was found between the expression levels of the gene ligands and their receptors in brain, BAT and testis suggesting a common pathway of different genes in these tissues in either male and female. Changes in the expression levels of osteocalcin, Ngf, or Bdnf genes may mutually affect the expression levels of the others. Moreover, it may be possible that different ligands may operate through different receptor subtypes. Oxt and Oxtr failed to show significant correlation. The up-regulation of Ngf /p75NTR in BAT is consistent

  7. The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency

    OpenAIRE

    Kok-Yong Chin; Saif Abdul-Majeed; Norazlina Mohamed; Soelaiman Ima-Nirwana

    2017-01-01

    Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The...

  8. Development of an enzyme-linked immunosorbent assay for detection of chicken osteocalcin and its use in evaluation of perch effects on bone remodeling in caged White Leghorns.

    Science.gov (United States)

    Jiang, S; Cheng, H W; Hester, P Y; Hou, J-F

    2013-08-01

    Osteocalcin (OC) is a sensitive biochemical marker for evaluating bone turnover in mammals. The role of avian OC is less clear because of the need for a chicken assay. Our objectives were to develop an assay using indirect competitive ELISA for detecting chicken serum OC and use the assay to examine the effects of perches on bone remodeling in caged hens. Anti-chicken OC polyclonal antibody was produced by immunization of rabbits with a recombinant OC from Escherichia coli. Chicken OC extracted from bone was used as a coated protein, and purified chicken OC was used for calibration. The limit of detection of the developed OC ELISA was 0.13 ng/mL. The intra- and interassay CV were chickens that never had access to perches during their life cycle. Treatment 2 chickens had perches during the pullet phase (0 to 16.9 wk of age), whereas treatment 3 chickens had perches only during the egg-laying phase of the life cycle (17 to 71 wk of age). Treatment 4 chickens always had access to perches (0 to 71 wk of age). Correlation between the 2 assays was 0.62 (P chicken ELISA were higher than that detected using the Rat-Mid ELISA (P chicken ELISA assay showed that hens with perch access had higher concentrations of serum OC than hens without perches during egg laying (P = 0.04). Pullet access to perches did not affect serum OC levels in 71-wk-old hens (P = 0.15). In conclusion, a chicken OC ELISA has been validated that is sensitive and accurate with adequate discriminatory power for measuring bone remodeling in chickens.

  9. Uncarboxylated Osteocalcin and Gprc6a Axis Produce Intratumoral Androgens in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2016-05-01

    None. Figure 5. Bone tumor growth of VCaP osteocalcin transfectants. A. Whole body mice luciferase imaging for bone tumors. B. Quantitation of...Figure 1). Conditioned media was collected from RFP, osteocalin and mutated Osteocalcin expressing cells. ELISA quatitiation show that...transfectants expressing RFP, Osteocalcin and 3E/Q osteocalcin cells were injected into tibae of mice. Mass spectrometric quantitation of Testosterone and

  10. Regulation of energy metabolism by the skeleton: osteocalcin and beyond.

    Science.gov (United States)

    Ferron, Mathieu; Lacombe, Julie

    2014-11-01

    The skeleton has recently emerged as an endocrine organ implicated in the regulation of glucose and energy metabolism. This function of bone is mediated, at least in part, by osteocalcin, an osteoblast-derived protein acting as a hormone stimulating insulin sensitivity, insulin secretion and energy expenditure. Osteocalcin secretion and bioactivity is in turn regulated by several hormonal cues including insulin, leptin, the sympathetic nervous system and glucocorticoids. Recent findings support the notion that osteocalcin functions and regulations are conserved between mice and humans. Moreover, studies in mice suggest that osteocalcin could represent a viable therapeutic approach for the treatment of obesity and insulin resistance. In this review, we summarize the current knowledge on osteocalcin functions, its various modes of action and the mechanisms implicated in the control of this hormone.

  11. Vitamin C prevents hypogonadal bone loss.

    Directory of Open Access Journals (Sweden)

    Ling-Ling Zhu

    Full Text Available Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.

  12. Pamidronate and zoledronate effects in the increment of bone mineral density and histomorphometry in rats Efeitos do pamidronato e zoledronato no incremento da densitometria óssea e histomorfometria em ratos

    Directory of Open Access Journals (Sweden)

    Antônio Fiel Cruz Júnior

    2011-04-01

    Full Text Available PURPOSE: To compare increment of bone mineral density (BMD with pamidronate, zoledronate and the isolated effect of proteinous diet in undernourished oophorectomized and non-oophorectomized female rats, besides validating BMD's indexes. METHODS: 60 young female Lewis rats were divided into five experimental groups and a control group, oophorectomized and non-oophorectomized. The administration of drugs were submitted to proteinous and aproteinous diets. The variables analyzed were weight, bone densitometry, histomorphometry and biochemical evolution. RESULTS: In weight evaluation, the first interval showed a statistically meaningful increase in oophorectomized sample. In densitometry evaluation, the first interval showed statistically meaningful decrease in four medicated groups and third showed a statistically meaningful increase in 2 non-oophorectomized groups. In laboratory evaluation, there were an increase of total proteins and globulin, decrease of alkaline phosphatase, phosphorus and calcium (except for the oophorectomized in four medicated groups and increase of phosphorus and calcium in 2 not medicated groups. In histomorphometric evaluation, the oophorectomized groups had smaller increment of BMD. CONCLUSIONS: The pamidronate and zoledronate have shown effectives in the increment of BMD. The proteinous diet itself possesses therapeutic effect in BMD though not significant compared with medicated animals. The results of histomorphometry allow validating BMD's indexes in this experimental model.OBJETIVO: Comparar o incremento de densidade mineral óssea (DMA com pamidronato, zoledronato e o efeito isolado de dieta protéica em ratas desnutridas ooforectomizadas e não ooforectomizadas, além de validar índices de DMA. MÉTODOS: 60 ratas jovens Lewis foram divididas em cinco grupos experimentais e um grupo controle, com e sem ooforectomia. A administração das drogas foi submetida às dietas protéica e aprotéica. As vari

  13. Vitamin K-dependent carboxylation of osteocalcin: friend or foe?

    Science.gov (United States)

    Osteocalcin originates from osteooblastic synthesis and is deposited into bone or released into circulation, where it correlates with histological measures of bone formation. The presence of three vitamin K-dependent gamma-carboxyglutamic acid (Gla) residues is critical for osteocalcin’s structure, ...

  14. Effect of strontium ranelate on the bone histomorphometry after weightlessness in rats%雷尼酸锶对尾悬吊大鼠骨组织形态计量学的影响

    Institute of Scientific and Technical Information of China (English)

    赖阿娜; 杨锐; 张振; 王梅; 陈容平; 周瑛; 黄震; 陈宏

    2011-01-01

    目的 观察雷尼酸锶(SR)对尾悬吊大鼠骨组织形态计量学的影响.方法 选用30只3月龄SPF级雄性SD大鼠,随机分为全程对照组(n=6)、尾悬吊时服用SR组(n=6)、尾悬吊后服用SR组(n=6)、全程服用SR组(n=6)和尾悬吊后对照组(n=6).8周(其中尾悬吊4周)后处死,取胫骨上端松质骨进行骨组织形态计量学观察.结果 与全程对照组比较,SR干预组静态参数[骨小梁面积百分数(%Tb.Ar)、骨小梁厚度(Tb.Th)、骨小粱数目(Th.N)、骨小梁分离度(Tb.Sp)]、骨形成参数[荧光标记周长百分率(%L.Pm)、单位骨小梁面积骨形成率(BFR/TV)、矿化沉积率(MAR)]及骨吸收参数单位骨小梁面积上的成骨细胞数(Oc.N)均无统计学差异.与尾悬吊后对照组比较,SR干预组Tb.Th、Th.N、%Tb.Ar增加,Tb.Sp减少,提示骨量增加,%L.Pm、BFR/TV、MAR等骨形成参数增加,骨吸收参数Oc.N降低,而SR干预各组间静态参数、骨形成参数及骨吸收参数均无统计学差异.结论 SR可明显改善尾悬吊大鼠骨组织形态计量学指标,对失重性骨质疏松有防治作用.%Objective To investigate the effect of strontium ranelate (SR) on the bone histomorphometry of tail-suspended rat.Methods Thirty male SD rats (3 months old) were randomly divided into five groups (6 each): rats in SR-1 group underwent tail suspension for 4 weeks and given SR simultaneously. In SR-2 group rats received tail suspension for 4 weeks and given SR thereafter. In SR-3 group rats underwent tail suspension for 4 weeks and given SR during the whole course. In control-1 group rats underwent tail suspension for 4 weeks and not given SR, and in control-2 group rats did not undergo tail suspension and were not given SR. Animals were sacrificed 8 weeks (including 4 weeks of tail suspension) later, and the cancellous bone of upper end of tibia was then analyzed histomorphologically. Results There were no significant differences between control-2 group and the 3 SR

  15. Biochemical markers of bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-08-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

  16. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry.

    Science.gov (United States)

    Balizs, Gabor; Weise, Christoph; Rozycki, Christel; Opialla, Tobias; Sawada, Stefanie; Zagon, Jutta; Lampen, Alfonso

    2011-05-05

    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C(18) or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  17. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Balizs, Gabor, E-mail: gabor.balizs@bfr.bund.de [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany); Weise, Christoph [Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, D-14195 Berlin (Germany); Rozycki, Christel; Opialla, Tobias; Sawada, Stefanie; Zagon, Jutta; Lampen, Alfonso [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany)

    2011-05-05

    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C{sub 18} or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  18. Acupuncture Increases Bone Strength by Improving Mass and Structure in Established Osteoporosis after Ovariectomy in Rats

    Institute of Scientific and Technical Information of China (English)

    WenPing Zhang; Masayuki Kanehara; YanJun Zhang; ZhiFeng Yu; GuoXia Zhang; YouXin Yang; Saori Tachi; Torao Ishida

    2006-01-01

    The effects of acupuncture on bone biomechanical properties and histomorphometry in ovariectomized (OVX) rats were studied. Twenty-four 8-week-old female Sprague-Dawley rats were randomly assigned to three groups: sham, model and acupuncture. Rats in the model and acupuncture groups were ovariectomized,while those in the sham group underwent a sham operation. All rats were anesthetized and fastened for 15minutes, and for the acupuncture group, needling on Pishu (BL20) and Shenshu (BL23) was performed.Blood and urine were collected to measure serum osteocalcin (OC) and urinary calcium, phosphorus or deoxypyridinoline (Dpd). After 16 weeks of treatment, all the rats were killed and their tibiae and femora were removed. The tibiae were used for analyses of bone histomorphometry and the femora for a three-point bending test. Acupuncture gave significant protection against ovariectomy-caused decline on femoral strength in the mechanical test, increased the trabecular bone volume and thickness, lowered the trabecular separation of tibiae and restricted the excretion of phosphorus and Dpd, while promoting the concentrations of serum osteocalcin as compared with model rats. These results seemed to indicate that acupuncture on the points of Pishu (BL20) and Shenshu (BL23) not only promoted the bone formation but also suppressed the bone resorption induced by OVX in osteoporotic rats, which suggests that it would be a potentially useful and convenient method in preventing osteoporosis.

  19. Vitamin D-3 and vitamin K-1 supplementation of Dutch postmenopausal women with normal and low bone mineral densities : effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin

    NARCIS (Netherlands)

    Schaafsma, A; Muskiet, FAJ; Storm, H; Hofstede, GJH; Pakan, [No Value; Van der Veer, E

    2000-01-01

    Objective: Improvement of vitamin D and K status of about 60-y-old postmenopausal Dutch women. Design: In a randomized study postmenopausal women with normal (T-score >-1; n = 96) and low (T-score less than or equal to-1; n = 45) bone mineral density (BMD) of the lumbar spine, were supplemented with

  20. Vitamin D-3 and vitamin K-1 supplementation of Dutch postmenopausal women with normal and low bone mineral densities : effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin

    NARCIS (Netherlands)

    Schaafsma, A; Muskiet, FAJ; Storm, H; Hofstede, GJH; Pakan, [No Value; Van der Veer, E

    2000-01-01

    Objective: Improvement of vitamin D and K status of about 60-y-old postmenopausal Dutch women. Design: In a randomized study postmenopausal women with normal (T-score >-1; n = 96) and low (T-score less than or equal to-1; n = 45) bone mineral density (BMD) of the lumbar spine, were supplemented with

  1. Effects of compound danshen extract on bone histomorphometry of high-fat rats%复方丹参对高脂大鼠模型骨形态计量学参数的影响**

    Institute of Scientific and Technical Information of China (English)

    张新乐; 吴铁; 崔燎; 许碧莲

    2013-01-01

      背景:复方丹参对抗泼尼松性大鼠的骨丢失具有抑制骨吸收作用,但对高脂血症所致的骨质疏松症效果如何未见报道。目的:通过骨形态计量学观察复方丹参对大鼠胫骨和腰椎骨丢失的防治作用。方法:用脂肪乳剂建立高脂血症骨丢失大鼠模型,30只SD大鼠随机数字表法分为3组,正常对照组、高脂乳剂组、复方丹参组,分别给予生理盐水、高脂乳剂、高脂乳剂和复方丹参,连续16周。结果与结论:与高脂乳剂组相比,复方丹参可使高脂大鼠胆固醇明显降低和高密度脂蛋白胆固醇明显升高,可以有效改善高脂乳剂导致的脂质代谢紊乱。复方丹参组的骨小梁面积百分数、骨小梁数量、成骨细胞贴壁长度百分率均增加(P <0.05),而骨小梁分离度、每毫米破骨细胞数、破骨细胞贴壁长度百分率均减少(P <0.01),反映骨形成及骨矿化的指标变化不明显;胫骨中段的皮质骨面积百分数增加(P <0.01),骨髓腔面积百分数减少(P<0.01),骨内外膜的形成和矿化均无明显变化;腰椎松质骨的骨小梁面积百分数、骨小梁数量、骨小梁宽度增加(P<0.05)、而骨小梁分离度减少(P<0.01)。提示长期高脂乳剂灌胃会导致大鼠骨量丢失,复方丹参能有效对抗高脂大鼠胫骨上段、中段骨、第5腰椎的骨丢失。%BACKGROUND:Compound danshen extract can inhibit bone resorption and rival bone loss of rats induced by prednisone. However, there are no reports indicating its effectiveness in osteoporosis induced by hyperlipidemia. OBJECTIVE:To study the effect of compound danshen extract against tibia and lumbar spine bone loss by using bone histomorphometry through establishing a osteoporosis rat model induced by high-fat emulsion. METHODS:Thirty 3-month-old male Sprague-Dawley rats were randomly divided into normal saline group, high-fat emulsion group, compound danshen extract

  2. Quantification of Osseointegration of Plasma-Polymer Coated Titanium Alloyed Implants by means of Microcomputed Tomography versus Histomorphometry

    Directory of Open Access Journals (Sweden)

    Carolin Gabler

    2015-01-01

    Full Text Available A common method to derive both qualitative and quantitative data to evaluate osseointegration of implants is histomorphometry. The present study describes a new image reconstruction algorithm comparing the results of bone-to-implant contact (BIC evaluated by means of µCT with histomorphometry data. Custom-made conical titanium alloyed (Ti6Al4V implants were inserted in the distal tibial bone of female Sprague-Dawley rats. Different surface configurations were examined: Ti6Al4V implants with plasma-polymerized allylamine (PPAAm coating and plasma-polymerized ethylenediamine (PPEDA coating as well as implants without surface coating. After six weeks postoperatively, tibiae were explanted and BIC was determined by µCT (3D and afterwards by histomorphometry (2D. In comparison to uncoated Ti6Al4V implants demonstrating low BIC of 32.4% (histomorphometry and 51.3% (µCT, PPAAm and PPEDA coated implants showed a nonsignificant increase in BIC (histomorphometry: 45.7% and 53.5% and µCT: 51.8% and 62.0%, resp.. Mean BIC calculated by µCT was higher for all surface configurations compared to BIC detected by histomorphometry. Overall, a high correlation coefficient of 0.70 (p<0.002 was found between 3D and 2D quantification of BIC. The μCT analysis seems to be suitable as a nondestructive and accurate 3D imaging method for the evaluation of the bone-implant interface.

  3. Effect of Epimedium-derived Phytoestrogen on Bone Turnover and Bone Microarchitecture in OVX-induced Osteoporotic Rats

    Institute of Scientific and Technical Information of China (English)

    Songlin PENG; Renyun XIA; Huang FANG; Feng LI; Anmin CHEN; Ge ZHANG; Ling QIN

    2008-01-01

    To investigate the preventive effect of epimedium-defivod phytoestrogen (PE) on osteoporosis induced by ovariectomy (OVX) in rats, 11-month-old female Wistar rats were randomly di- vided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE (0.4 g·kg-1·day·-1) started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) for bone turnover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabeonlar bone structure and then bone histomorphometry was per- formed to assess bone remodeling. The OVX rats were in a high bone turnover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trahecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indi- cated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

  4. Effects of 2-deoxy-D-glucose and quercetin on the gene expression of bone sialoprotein and osteocalcin during the differentiation in irradiated MC3T3-E1 osteoblastic cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Un; Kim, Kyoung A; Koh, Kwang Jun [Department of Oral and Maxillofacial Radiology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2009-09-15

    To investigate the effects of 2-deoxy-D-glucose (2-DG) and quercetin (QCT) on gene expression of bone sialoprotein (BSP) and osteocalcin (OC) during the differentiation in irradiated MC3T3-E1 osteoblastic cells. When MC3T3-E1 osteoblastic cells had reached 70-80% confluence, cultures were transferred to a differentiating medium supplemented with 5 mM 2-DG or 10 {mu}M QCT, and then irradiated with 2, 4, 6, and 8 Gy. At various times after irradiation, the cells were analyzed for the synthesis of type I collagen, and expression of BSP and OC. The synthesis of type I collagen in cells exposed to 2 Gy of radiation in the presence of 2-DG or QCT showed no significant difference compared with the control group within 15 days post-irradiation. When the cells were irradiated with 8 Gy, 2-DG facilitated the irradiation mediated decrease of type I collagen synthesis, whereas such decrease was inhibited by treating with QCT. During MC3T3-E1 osteoblastic cell differentiation, the mRNA expression of BSP and OC showed the peak value at 14 days and 21 days, respectively. 2-DG or QCT treatment alone decreased the level of BSP mRNA, but increased the OC mRNA level only at early time of differentiation (day 7). In the cells irradiated with 2, 4, 8 Gy, the mRNA expression of BSP and OC decreased at 7 days after the irradiation. The cells were treated with various dose of radiation in the presence of 2-DG or QCT, the mRNA level of both BSP and OC increased although this increase was observed at low dose of radiation (2 Gy) and at the early stage of differentiation. However, when the cells were exposed to 4, 6, or 8 Gy, the increase of BSP and OC mRNAs was detected only in cells co-incubated with QCT. This study demonstrates that 2-DG and QCT affect differently the expression of bone formation related factors, type I collagen, BSP, and OC in the irradiated MC3T3-E1 osteoblasic cells, according to the dose of radiation and the times of differentiation. Overall, the present findings

  5. Vertebral histomorphometry in a child with glucocorticoid-induced osteoporosis.

    Science.gov (United States)

    Hatakeyama, Yuji; Miyakoshi, Naohisa; Kasukawa, Yuji; Watanabe, Arata; Hirayama, Masashi; Senma, Seietsu; Ono, Iwao; Shimada, Yoichi

    2012-08-01

    Vertebral fractures are an under-recognized problem in children with glucocorticoid-induced osteoporosis (GIO). They cause severe back pain and spinal column deformity with a decrease of quality of life. For evaluating the bone mass, bone mineral density measurements have been widely carried out using dual energy X-ray absorptiometry. However, bone histomorphometric analyses of GIO in children are scarce. Bone histomorphometric analyses of vertebral bodies have not been reported. Our aim is to report the first bone histomorphometric data for vertebrae from an autopsied child with GIO. A 15-year-old girl with systemic lupus erythematosus was started on a daily oral dose of 10 mg of prednisolone at 6 years of age. She presented with back pain from 12 years of age. Magnetic resonance imaging at 14 years of age showed a compression fracture of the first lumbar (L1) vertebral body. At 15 years of age, she died of heart failure owing to pulmonary hypertension. Collapsed (L1) and non-collapsed (seventh thoracic vertebrae; T7) vertebral bodies were autopsied for bone histomorphometry and compared. T7 showed severe osteoporosis (bone volume, 4.99%; trabecular thickness, 59 µm; trabecular separation, 1,134 µm). Compared with T7, L1 showed increased bone volume (33.9%) and trabecular thickness (77 µm), and decreased trabecular separation (156 µm) owing to the impact of the vertebral fracture. The bone formation and bone resorption parameters were comparable between the two vertebrae. These histological findings suggest that severe osteoporosis developed after long-term glucocorticoid administration, and that the remodeling activities were similar in the fractured and non-fractured vertebrae.

  6. Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Gupte, Anisha A; Sabek, Omaima M; Fraga, Daniel; Minze, Laurie J; Nishimoto, Satoru K; Liu, Joey Z; Afshar, Solmaz; Gaber, Lillian; Lyon, Christopher J; Gaber, A Osama; Hsueh, Willa A

    2014-12-01

    Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr(-/-) mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.

  7. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to expressions of c-fos and c-jun products and bone matrix proteins: a clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I collagen, osteonectin, osteopontin, and osteocalcin.

    Science.gov (United States)

    Sakamoto, A; Oda, Y; Iwamoto, Y; Tsuneyoshi, M

    1999-12-01

    Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. We retrospectively studied clinicopathologic findings in 62 cases of fibrous dysplasia and 20 cases of osteofibrous dysplasia with regard to their anatomic location and histological appearance. From among these cases, the immunohistochemical expressions of c-fos and c-jun proto-oncogene products and bone matrix proteins of type I collagen, osteonectin, osteopontin, and osteocalcin were evaluated in 20 typical fibrous dysplasias and 17 osteofibrous dysplasias using paraffin sections, and these expressions were then assessed semiquantitatively. Microscopically, fibrous dysplasia showed various secondary changes, such as hyalinization, hemorrhage, xanthomatous reaction, and cystic change in 22 of the 62 cases (35%). This was a higher incidence than in osteofibrous dysplasia, in which only 2 of the 20 cases (10%) showed such changes. In the elderly fibrous dysplasia cases, the cellularity of fibroblast-like cells was rather low, and those cases were hyalinized. Almost all of the cases of fibrous dysplasia and osteofibrous dysplasia showed positive expressions of c-fos and c-jun products. The expressions of type I collagen and osteopontin showed no difference between fibrous dysplasia and osteofibrous dysplasia. Immunoreactivity for osteonectin in bone matrix was detected in only 1 case of fibrous dysplasia (1 of 20), whereas it was recognized in 14 of the 17 cases of osteofibrous dysplasia. Furthermore, the immunoreactivity for osteocalcin in bone matrix and fibroblast-like cells was higher in fibrous dysplasia than it was in osteofibrous dysplasia, semiquantitatively. Our immunohistochemical results regarding osteonectin and osteocalcin suggest that the bone matrix of fibrous dysplasia is

  8. Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice.

    Science.gov (United States)

    Hankenson, K D; James, I E; Apone, S; Stroup, G B; Blake, S M; Liang, X; Lark, M W; Bornstein, P

    2005-08-01

    Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption.

  9. Plasma levels of osteocalcin and retinol binding protein-4 in patients with medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Jabar Lotfi

    2014-04-01

    Conclusion: According to difference between plasma levels of osteocalcin and retinol binding protein-4 in patients suffered of medullary thyroid carcinoma comparison with normal subjects, it can be said that, probably medullary thyroid carcinoma has effect on bone and adipose tissue metabolism, so osteocalcin and retinol binding protein-4 hormones have potential to be used for confirmation of diagnosis or following treatment of medullary thyroid carcinoma.

  10. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kover, Karen, E-mail: kkover@cmh.edu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  11. Effects of Adding Ipriflavone to Low-calcium Diet on Microstructure and Histomorphometry of Bone in Cage Layers%低钙日粮添加依普黄酮对笼养蛋鸡骨组织显微结构和形态计量学的影响

    Institute of Scientific and Technical Information of China (English)

    吕文亭; 马利芹; 杨永红; 王鹏; 利凯

    2012-01-01

    This experiment was conducted to study the effects of adding Ipriflavone to low-calcium diet on microstructure and histomorphometry of bone in hyline brown laying hens. Two hundred 24-week-old hyline brown laying hens were randomly divided into four groups and fed on diets as follows; control group (containing calcium 3. 55% in basic diet)? low calcium group (containing calcium 1. 27% in low-calcium diet) , test group I (adding 8 mg o kg-1 Ipriflavone to low-calcium diet) and test group II (adding 20 mg o kg-1 Ipriflavone to low-calcium diet) for 60 days. At the end of experiment, 10 hens in each group were killed. Then, demineralized bone sections of the left middle tibias were made for observing the changes of bone microstructure by using OLYMPUS BX41 metalloscope, and some static parameters of bone histomorphometry were measured by Image-Pro Plus 6. 0. Tibia microstructure was observed. Compared with control group, cortical bone of low calcium group had many resorption cavities, there were a large number of osteo-clasts in the resorption cavities, and osteoclasts increased in the surface of medullary bone trabeculas, the effect of bone resorption was more than that of bone formation and led to osteoporosis. Cortical bone of test group I had many resorption cavities, there were more osteoclasts in the resorption cavities and the surface of medullary bone trabeculas, the effect of bone resorption was not inhibited. There were a large number of osteogenic cells and osteoblasts in the outer surface of cortical bone in test group II, the effect of bone formation was increased. And, Static parameters of bone histomorphometry were measured. Compared with low calcium group, Tb. Ar and %Tb. Ar in test group I and II were very significantly increased (P0. 05). In test group II Tb. Sp was significantly decreased (P<0. 05) and Tb. Th was significantly increased (P< 0. 05). The results showed that adding 20 mg ?kg-1 Ipriflavone to low-calcium diet strengthened bone

  12. 骨碎补总黄酮对去卵巢大鼠腰椎松质骨骨形态计量学参数的影响%Effect of drynaria fortunei flavonoids on bone histomorphometry parameters of lumbar cancellous bone in ovariectomized rat

    Institute of Scientific and Technical Information of China (English)

    陈海啸; 梁军波; 伍海昭

    2011-01-01

    目的:研究骨碎补总黄酮对去卵巢大鼠腰椎松质骨骨形态计量学参数的影响.方法:将40只SD大鼠随机分为4组:假切除组(A组)、模型组(B组)、倍美力组(C组)、骨碎补组(D组),每组10只.麻醉后B、C、D组从背部入路切除双侧卵巢;A组仅切除腹部少许脂肪.造模后第2天开始,A、B组标准饲料常规饲养;C组在标准饲料常规喂养的同时,每天灌服倍美力悬剂2mL(按人鼠体表面积换算,相当于倍美力0.017mg);D组在标准饲料喂养的同时,每天灌服中药浓缩剂2mL(按人鼠体表面积换算,相当于骨碎补总黄酮0.02g).6个月后取大鼠的L2椎体进行骨形态计量学检查.结果:4组大鼠骨体积分数、骨小梁厚度、骨小梁间距、骨小梁节点数及游离末端数比较,差异均有统计学意义(F=4.031,P=0.043;F=3.980,P=0.045;F=4.133,P=0.041;F=4.091,P=0.043;F=4.382,P=0.041).同一指标组间比较:①B组骨体积分数低于A、C、D组(LSD-t=3.322,P=0.011;LSD-t=2.861,P=0.019;LSD-t=3.023,P20.015);②B组骨小梁厚度低于A、C、D组(125D-t=3.360,P=0.011;LSD-t=2.925,P=0.019;LSD-t=3.066,P=0.017);③B组骨小梁间距大于A、C、D组(LSD-t=3.417,P=0.011;LSD-t=2.981,P=0.019;LSD-t=3.108,P=0.013);④B组骨小梁节点数少于A、C、D组(LSD-t=4.191,P=0.080;LSD-t=2.956,P=0.039;LSD-t=2.632,P=0.045);⑤B组骨小梁游离末端数大于A、C、D组(LSD-t=4.021,P=0.008;LSD-t=2.237,P=0.048;LSD-t=2.510,P=0.038);⑥C组与D组骨体积分数、骨小梁厚度、骨小梁间距、骨小梁节点数、骨小梁游离末端数比较,差异均无统计学意义(LSD-t=0.138,P=0.868;LSD-t=0.116,P=0.901;LSD-t=0.186,P=0.712;LSD-t=0.239,P=0.611;LSD-t=0.381,P=0.589).结论:骨碎补总黄酮能通过增加骨量、改善骨三维结构,从而增强骨强度.%Objective:To study the effect of drynaria fortunei flavonoids on bone histomorphometry parameters of lumbar cancellous bone in ovariectomized rat. Methods:40 SD rats were randomly divided into 4

  13. Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Yu-Tzu Tsao

    2017-01-01

    Full Text Available There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.

  14. Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels.

    Science.gov (United States)

    Guidon, P T; Salvatori, R; Bockman, R S

    1993-01-01

    Gallium nitrate, a group IIIa metal salt, has been found to be clinically effective for the treatment of accelerated bone resorption in cancer-related hypercalcemia and Paget's disease. Here we report the effects of gallium nitrate on osteocalcin mRNA and protein levels on the rat osteoblast-like cell line ROS 17/2.8. Gallium nitrate reduced both constitutive and vitamin D3-stimulated osteocalcin protein levels in culture medium by one-half and osteocalcin mRNA levels to one-third to one-tenth of control. Gallium nitrate also inhibited vitamin D3 stimulation of osteocalcin and osteopontin mRNA levels but did not affect constitutive osteopontin mRNA levels. Among several different metals examined, gallium was unique in its ability to reduce osteocalcin mRNA levels without decreasing levels of other mRNAs synthesized by ROS 17/2.8 cells. The effects of gallium nitrate on osteocalcin mRNA and protein synthesis mimic those seen when ROS 17/2.8 cells are exposed to transforming growth factor beta 1 (TGF beta 1); however, TGF-beta 1 was not detected in gallium nitrate-treated ROS 17/2.8 cell media. Use of the RNA polymerase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that gallium nitrate did not alter the stability of osteocalcin mRNA. Transient transfection assays using the rat osteocalcin promoter linked to the bacterial reporter gene chloramphenicol acetyltransferase indicated that gallium nitrate blocked reporter gene expression stimulated by the osteocalcin promoter. This is the first reported effect of gallium nitrate on isolated osteoblast cells.

  15. Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis.

    Science.gov (United States)

    Thamsborg, G; Jensen, J E; Kollerup, G; Hauge, E M; Melsen, F; Sorensen, O H

    1996-02-01

    The effect of nasal salmon calcitonin (SCT) on bone has been investigated by densitometry, biochemical markers of bone turnover, and histomorphometry. 62 women (mean age 65 years) who had experienced Colles' fracture after menopause were randomized to receive either nasal salmon calcitonin (SCT) 200 IU or nasal placebo daily for 24 months. All received a daily supplement of 0.5 g calcium. There was a significant increase above baseline in the bone mineral density of the lumbar spine in the SCT group (2.5%; 95% confidence interval 0.9--4.2%) and in the placebo group (1.7%; 95% confidence interval 0.3--3.1%) after 24 months, but the difference between the groups was not significant (0.8%; 95% confidence interval -1.2-3.0%). Serum levels of osteocalcin decreased significantly below baseline in the SCT group, whereas they were unchanged in the placebo group. At months 12 and 24, serum levels of osteocalcin were significantly lower in the SCT group than in the placebo group (p transient decrease was observed in the placebo group. The differences between the groups were, however, not significant. The erosion depth was significantly lower in the SCT group than in the placebo group after 12 months (median [interquartile range]; 46.9 mu m [10.4] vs. 50.5 mu m [10.7]; p = 0.03), whereas bone volume and activation frequency did not differ between the groups. This study indicates that nasal SCT in a dose of 200 IU daily induces only a minor inhibition of bone resorption and therefore produces only a minor increase in bone mass. Furthermore, it seems that nasal SCT in a dose of 200 IU does not interfere with the recruitment of new bone multicellular units, but preferably decreases ongoing osteoclastic bone resorption.

  16. Investigation of the protein osteocalcin of Camelops hesternus: Sequence, structure and phylogenetic implications

    Science.gov (United States)

    Humpula, James F.; Ostrom, Peggy H.; Gandhi, Hasand; Strahler, John R.; Walker, Angela K.; Stafford, Thomas W.; Smith, James J.; Voorhies, Michael R.; George Corner, R.; Andrews, Phillip C.

    2007-12-01

    Ancient DNA sequences offer an extraordinary opportunity to unravel the evolutionary history of ancient organisms. Protein sequences offer another reservoir of genetic information that has recently become tractable through the application of mass spectrometric techniques. The extent to which ancient protein sequences resolve phylogenetic relationships, however, has not been explored. We determined the osteocalcin amino acid sequence from the bone of an extinct Camelid (21 ka, Camelops hesternus) excavated from Isleta Cave, New Mexico and three bones of extant camelids: bactrian camel ( Camelus bactrianus); dromedary camel ( Camelus dromedarius) and guanaco ( Llama guanacoe) for a diagenetic and phylogenetic assessment. There was no difference in sequence among the four taxa. Structural attributes observed in both modern and ancient osteocalcin include a post-translation modification, Hyp 9, deamidation of Gln 35 and Gln 39, and oxidation of Met 36. Carbamylation of the N-terminus in ancient osteocalcin may result in blockage and explain previous difficulties in sequencing ancient proteins via Edman degradation. A phylogenetic analysis using osteocalcin sequences of 25 vertebrate taxa was conducted to explore osteocalcin protein evolution and the utility of osteocalcin sequences for delineating phylogenetic relationships. The maximum likelihood tree closely reflected generally recognized taxonomic relationships. For example, maximum likelihood analysis recovered rodents, birds and, within hominins, the Homo-Pan-Gorilla trichotomy. Within Artiodactyla, character state analysis showed that a substitution of Pro 4 for His 4 defines the Capra-Ovis clade within Artiodactyla. Homoplasy in our analysis indicated that osteocalcin evolution is not a perfect indicator of species evolution. Limited sequence availability prevented assigning functional significance to sequence changes. Our preliminary analysis of osteocalcin evolution represents an initial step towards a

  17. 儿童阻塞性睡眠呼吸暂停低通气综合征患者骨龄和血清骨钙素的测定分析%Determination and analysis of serum osteocalcin and bone age in children with obstructive sleep apnea hypopnea syndrome

    Institute of Scientific and Technical Information of China (English)

    李文丽; 冯慧伟; 张辉; 张海令; 张红萍; 范献良

    2012-01-01

    Objective To study the influence of obstructive sleep apnea hypopnea syndrome on children's growth, especially on their bone growth, by the determinations and analysis of the serum osteocalcin level and bone age, including height, weight and an other parameters. Methods 29 children, diagnosed as OSAHS according to their history, physical examination and polysomnography, were enrolled in the experimental group and the another 13 children without sleep snoring and dyspnoea were enrolled into the control group. Anteroposterior (AP) X-ray film was taken of the left wrist to assess bone age, and the serum osteocalcin was measured in a fasting blood sample. Also, the height and weight data of children were measured. Results The bone age in the experimental and control group were 6.31 +1.12, and 6.45 + 1. 57 years, respectively (t = 0. 15, P > 0.05). The D-values in the bone age and the real age for the two groups showed a significant difference (t= 8. 07, P < 0.05). The serum osteocalcin was 7.41 + 0. 31 μg/L in the experimental group, and 10. 22 + 0. 50 μg/L in the control group (t = 10. 17, P < 0. 05). Conclusion Compared with the controls, the bone age of children with OSAHS was lower and the serum osteocalcin level was decreased, which indicated that OSAHS probably exerts influence on bone growth.%目的 通过对阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患儿骨龄、血清骨钙素水平、身高、体质量等参数的测定分析,探讨OSAHS对儿童患者生长发育,尤其是对骨骼生长发育的影响.方法 根据就诊儿童病史、症状、体征及多导睡眠仪监测结果,选择OSAHS患儿29例为实验组,同时选择无睡眠打鼾和呼吸障碍的健康儿童13例作为对照组.两组儿童均拍摄左手正位X线片测算骨龄,抽取空腹血测定血清骨钙素水平,同时对身高、体质量等指标进行测算.结果 OSAHS实验组骨龄(6.31±1.12)岁,对照组骨龄(6.45±1.57)岁,差异无统计学意义(t=0.15,P>0

  18. Hormone-sensitive lipase-knockout mice maintain high bone density during aging.

    Science.gov (United States)

    Shen, Wen-Jun; Liu, Li-Fen; Patel, Shailja; Kraemer, Fredric B

    2011-08-01

    We tested the hypothesis that the actions of hormone-sensitive lipase (HSL) affect the microenvironment of the bone marrow and that removal of HSL function by gene deletion maintains high bone mass in aging mice. We compared littermate control wild-type (WT) and HSL(-/-) mice during aging for changes in serum biochemical values, trabecular bone density using micro-computed tomography, bone histomorphometry, and characteristics of primary bone marrow cells and preosteoblasts. There is a regulated expression of HSL and genes involved in lipid metabolism in the bone marrow during aging. HSL(-/-) mice have increased serum levels of insulin and osteocalcin with decreased leptin levels. Compared with the marked adipocyte infiltration in WT bone marrow (65% by area) at 14 mo, HSL(-/-) mice have fewer (16%, PHSL(-/-) mice maintain a higher bone density (bone volume/total volume 6.1%) with age than WT mice (2.6%, PHSL(-/-) mice show increased growth rates and higher osteogenic potential, manifested by increased expression of Runx2 (3.5-fold, PHSL directs cells within the bone marrow toward osteoblast differentiation and favors the maintenance of bone density with aging.

  19. Structural evidence of a fourth Gla residue in fish osteocalcin: biological implications.

    Science.gov (United States)

    Frazão, Carlos; Simes, Dina C; Coelho, Ricardo; Alves, Dora; Williamson, Matthew K; Price, Paul A; Cancela, M Leonor; Carrondo, Maria A

    2005-02-01

    Osteocalcin is a small (45 amino acids) secreted protein found to accumulate in bone and dentin of many organisms by interacting with calcium and hydroxyapatite, through the presence of three gamma-carboxylated residues. In this work, we describe the first X-ray crystal structure for a nonmammalian osteocalcin, obtained at 1.4 A resolution, purified from the marine teleost fish Argyrosomus regius. The three-dimensional fit between the A. regius structure and that of the only other known X-ray structure, the porcine osteocalcin, revealed a superposition of the Calpha atoms of their metal chelating residues, Gla and Asp, showing that their spatial distribution is consistent with the interatomic distances of calcium cations in the hydroxyapatite crystals. In both structures, the protein forms a tight globular arrangement of their three alpha-helices while the remaining residues, at N- and C-terminal regions, have essentially no secondary structure characteristics. This study revealed the presence of a fourth gamma-carboxylation at Glu(25), not previously detected in the structure of the porcine osteocalcin or in any other of the sequentially characterized mammalian osteocalcins (human, cow, and rat). A confirmation of the fourth Gla residue in A. regius osteocalcin was achieved via LC-MS analysis. These four doubly charged residues are, together with Asp(24), concentrated in a common surface region located on the same side of the molecule. This further suggests that the known high affinity of osteocalcin for bone mineral may be derived from the clustering of calcium binding sites on this surface of the molecules.

  20. Spaceflight and age affect tibial epiphyseal growth plate histomorphometry

    Science.gov (United States)

    Montufar-Solis, Dina; Duke, Pauline J.; Durnova, G.

    1992-01-01

    Growth plate histomorphometry of rats flown aboard the Soviet biosatellite Cosmos 2044, a 14-day spaceflight, was compared with that of control groups. In growth plates of flight animals, there was a significant increase in cell number per column and height of the proliferative zone and a reduction in height and cell number in the hypertrophy/calcification zone. No significant differences were found in matrix organization at the ultrastructural level of flight animals, indicating that although spacefligfht continues to affect bone growth of 15-wk-old rats, extracellular matrix is not altered in the same manner as seen previously in younger animals. All groups showed growth plate characteristics attributed to aging: lack of calcification zone, reduced hypertrophy zone, and unraveling of collagen fibrils. Tail-suspended controls did not differ from other controls in any of the parameters measured. The results suggest that growth plates of older rats are less responsive to unloading by spaceflight or suspension than those of younger rats and provide new evidence about the modifying effect of spaceflight on the growth plate.

  1. Resveratrol as anti-aging therapy for age-related bone loss.

    Science.gov (United States)

    Tresguerres, Isabel F; Tamimi, Faleh; Eimar, Hazem; Barralet, Jake; Torres, Jesús; Blanco, Luis; Tresguerres, Jesús A F

    2014-10-01

    Previous studies have indicated that resveratrol, a natural phytoestrogen, can act as an anti-aging therapy to resist age-related changes of several body tissues. However, the anti-aging effects of resveratrol on bone have been poorly investigated in this natural aging population. Accordingly, this study was design to evaluate the effects of resveratrol on bone mass and biomechanical properties in old rat femora. Twenty 22-month-old male Wistar rats were divided into two randomly assigned groups (n=10). The first group was treated for 10 weeks with resveratrol (10 mg/kg per day) and the second group was left untreated (control). Rat femora were collected. Bone mass and bone microestructure were investigated by microcomputed tomography and histomorphometry. Biomechanical properties were determined by a three-point bending test. Plasma levels of CTX (carboxy-terminal telopeptide of type I collagen) and osteocalcin were also determined. Statistical analyses were performed by a Student two-tailed unpaired t-test. In all experiments, a value of p<0.05 was considered significant. Microcomputed tomography analyses demonstrated that resveratrol-treated rats had significant higher bone volume, bone trabecular number, and cortical thickness and lower spacing between trabeculae in comparison to the control group. Histomorphometric analyses confirmed the increase of bone volume in resveratrol-treated rats compared to controls. Resveratrol-treated rats had significant higher bone flexural modulus, stiffness, and ultimate load compared to control group. Treatment was not associated with changes in plasma CTX or osteocalcin. These findings demonstrate that resveratrol increases bone microstructure and bone mechanical properties in old male rats, suggesting that resveratrol might be used as anti-aging therapy to resist age-induced bone loss.

  2. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism

    Directory of Open Access Journals (Sweden)

    Eibhlís M. O'Connor

    2017-03-01

    Full Text Available The role of vitamin K in the body has long been associated with blood clotting and coagulation. In more recent times, its role in a range of physiological processes has been described including the regulation of bone and soft tissue calcification, cell growth and proliferation, cognition, inflammation, various oxidative processes and fertility, where osteocalcin is thought to up-regulate the synthesis of the enzymes needed for the biosynthesis of testosterone thereby increasing male fertility. Vitamin K dependent proteins (VKDP contain γ-carboxyglutamic acid residues which require post-translational, gamma-glutamyl carboxylation by the vitamin K-dependent (VKD gamma-glutamyl carboxylase enzyme for full functionality. These proteins are present both hepatically and extrahepatically. The role of bone-derived osteocalcin has many physiological roles including, maintenance of bone mass with more recent links to energy metabolism due to the role of the skeleton as an endocrine organ. It has been proposed that insulin binds to bone forming cells (osteoblasts promoting osteocalcin production which in turn promotes β-cell proliferation, insulin secretion and glucose control. However much of this research has been conducted in animal models with equivocal findings in human studies. This review will discuss the role of osteocalcin in relation to its role in human health, focusing specifically on glucose metabolism.

  3. Sclerostin antibody stimulates bone regeneration after experimental periodontitis.

    Science.gov (United States)

    Taut, Andrei D; Jin, Qiming; Chung, Jong-Hyuk; Galindo-Moreno, Pablo; Yi, Erica S; Sugai, James V; Ke, Hua Z; Liu, Min; Giannobile, William V

    2013-11-01

    The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl-Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature-induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl-Ab (+EP) or vehicle (+/- EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl-Ab to regenerate bone around tooth-supporting osseous defects. 3 and 6 wks after the initiation of Scl-Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro-computed tomography (micro-CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl-Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl-Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl-Ab treatment groups. Scl-Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl-Ab therapy in this and other oral bone defect disease scenarios.

  4. Cthrc1 is a positive regulator of osteoblastic bone formation.

    Directory of Open Access Journals (Sweden)

    Hiroaki Kimura

    Full Text Available BACKGROUND: Bone mass is maintained by continuous remodeling through repeated cycles of bone resorption by osteoclasts and bone formation by osteoblasts. This remodeling process is regulated by many systemic and local factors. METHODOLOGY/PRINCIPAL FINDINGS: We identified collagen triple helix repeat containing-1 (Cthrc1 as a downstream target of bone morphogenetic protein-2 (BMP2 in osteochondroprogenitor-like cells by PCR-based suppression subtractive hybridization followed by differential hybridization, and found that Cthrc1 was expressed in bone tissues in vivo. To investigate the role of Cthrc1 in bone, we generated Cthrc1-null mice and transgenic mice which overexpress Cthrc1 in osteoblasts (Cthrc1 transgenic mice. Microcomputed tomography (micro-CT and bone histomorphometry analyses showed that Cthrc1-null mice displayed low bone mass as a result of decreased osteoblastic bone formation, whereas Cthrc1 transgenic mice displayed high bone mass by increase in osteoblastic bone formation. Osteoblast number was decreased in Cthrc1-null mice, and increased in Cthrc1 transgenic mice, respectively, while osteoclast number had no change in both mutant mice. In vitro, colony-forming unit (CFU assays in bone marrow cells harvested from Cthrc1-null mice or Cthrc1 transgenic mice revealed that Cthrc1 stimulated differentiation and mineralization of osteoprogenitor cells. Expression levels of osteoblast specific genes, ALP, Col1a1, and Osteocalcin, in primary osteoblasts were decreased in Cthrc1-null mice and increased in Cthrc1 transgenic mice, respectively. Furthermore, BrdU incorporation assays showed that Cthrc1 accelerated osteoblast proliferation in vitro and in vivo. In addition, overexpression of Cthrc1 in the transgenic mice attenuated ovariectomy-induced bone loss. CONCLUSIONS/SIGNIFICANCE: Our results indicate that Cthrc1 increases bone mass as a positive regulator of osteoblastic bone formation and offers an anabolic approach for the

  5. 补充水解胶原蛋白与跑台运动联合作用对生长期大鼠骨密度和组织形态计量学指标的影响%Effects of combination of supplemental hydrolyzed collagen with treadmill exercise on bone mineral density and histomorphometry indexes in growing rats

    Institute of Scientific and Technical Information of China (English)

    马涛; 苏红燕

    2016-01-01

    Objective:This study aimed to explore effective ways to promote growth of growing bone from supplement hydrolyzed collagen and treadmill exercise.Methods:Forty-eight male SD rats,4 weeks of age,were randomly divided into six groups and assigned as follows:normal control group (CON),6%HC supplemented group (HC6),12%HC supplemented group (HC12),treadmill ex-ercise group (CON+Ex),6%HC +supplement treadmill exercise group (HC6+Ex)and 12%HC+supplement treadmill exercise group (HC12 +Ex),each group of eight rats.Rats treadmill trained speed is 30m/min,eight weeks of training,training six days a week,60 minutes a day of training.After eight weeks,bone mineral density and morphological indicators of femur and histo-morphometry indexes of tibia cancellous bone in each group were tested.Results:Compared with the corresponding control groups,bone mineral density and morphological indicators of femur and histo-morphometry indexes of tibia cancellous bone in supplemented HC group and the exercise group were significantly increased.Compared with moderate -dose HC supplements group,the difference of these indexes in high-dose HC supplement group were not statistically significant.Compared with simply HC supplement group and simply treadmill training group,these indexes in combined HC supplement with treadmill training group were significantly increased.Conclusion:Supplementary HC and treadmill exercise both can effectively promote growth of growing bone.Moderate doses of HC supplement can better promote growth of growing bone,high -dose supplementation did not play better results.HC supplement with treadmill exercise have a synergistic effect,the effect is better than simply HC supplements and simply treadmill exercise.%目的:从补充水解胶原蛋白(hydrolyzed collagen,HC)和跑台运动两个方面探索促进生长期骨生长的有效途径。方法:4周龄雄性SD大鼠48只,随机分为6组,每组8只:正常对照组(CON)、6%HC补充组(HC6

  6. The 1H NMR Structure of Bovine Pb2+- Osteocalcin and Implications for Lead Toxicity

    OpenAIRE

    Dowd, T. L.; Li, L.; Gundberg, C.M.

    2008-01-01

    Structural information on the effect of Pb2+ on proteins under physiologically relevant conditions is largely unknown. We have previously shown that low levels of lead increased the amount of osteocalcin bound to hydroxyapatite (BBA 1535:153)). This suggested that lead induced a more compact structure in the protein. We have determined the 3D structure of Pb2+-osteocalcin (49 amino acids), a bone protein from a target tissue, using 1H 2D NMR techniques. Lead, at a stoichiometry of only 1:1, i...

  7. 骨钙素在BMP2/7异源二聚体诱导种植体周围骨缺损再生中的表达%Expression of osteocalcin using rhBMP2/7 heterodimer in peri-implant bone defects compared to BMP2 homodimer and BMP7 homodimer

    Institute of Scientific and Technical Information of China (English)

    孙平; 王利民; 冯剑颖

    2011-01-01

    目的:研究骨钙素在使用BMP2/7异源二聚体促进种植体周骨缺损再生中的表达.方法:建立小型猪种植体周骨缺损模型,并使用BMP2/7异源二聚体及BMP2、BMP7同源二聚体促进骨再生,采用免疫组化方法分别在2、3、6周时检测新骨中骨钙素表达.结果:在各实验组中,骨钙素3周时表达达到最高值.在2、3、6周,BMP2/7组骨钙素表达均强于BMP2、BMP7同源二聚体组及对照组.结论:在以同样较低浓度(30ng/ml)作用于小型猪种植体周骨缺损诱导新骨形成过程中,BMP2/7异源二聚体较BMP、BMP7同源二聚体有效促进骨钙素的表达.%To delineate expression of osteocalcin induced by recombinant human bone morphogenetic protein (BMP)2/7 heterodimer in peri-implant bone defects in comparison to BMP2 and BMP7 homodimer.Methods: Identical peri-implant bone defects were created on the frontal skull of minipig. Collagen sponges with the same dose BMP2/7 heterodimer、 BMP2 homodimer 、 BMP7 homodimer 、 or BMPs were adopted to treat the freshly created implant bed. Titanium implants were centrally implanted with 4mm-flxture within bone defects. Immunohistochemical method was applied to evaluate the expression of osteocalcin (OCN) after 2, 3, and 6 weeks of implantation. Results: The OCN proteins displayed intensity peaks at 3 weeks (P<0.05) in all the groups. Immunoreactive expression of OCN of BMP2/7 group was more intensity than BMP2、 BMP7 and control group at 2, 3, and 6 weeks post-operation (P<0.05). Conclusions: Purified recombinant human BMP2/7 heterodimer can enhance the expression of OCN with significant differences over BMP2 homodimers or BMP7 homodimers with the same low-dose (30ng/ml).

  8. Matrix Gla protein and osteocalcin: from gene duplication to neofunctionalization.

    Science.gov (United States)

    Cancela, M Leonor; Laizé, Vincent; Conceição, Natércia

    2014-11-01

    Osteocalcin (OC or bone Gla protein, BGP) and matrix Gla protein (MGP) are two members of the growing family of vitamin K-dependent (VKD) proteins. They were the first VKD proteins found not to be involved in coagulation and synthesized outside the liver. Both proteins were isolated from bone although it is now known that only OC is synthesized by bone cells under normal physiological conditions, but since both proteins can bind calcium and hydroxyapatite, they can also accumulate in bone. Both OC and MGP share similar structural features, both in terms of protein domains and gene organization. OC gene is likely to have appeared from MGP through a tandem gene duplication that occurred concomitantly with the appearance of the bony vertebrates. Despite their relatively close relationship and the fact that both can bind calcium and affect mineralization, their functions are not redundant and they also have other unrelated functions. Interestingly, these two proteins appear to have followed quite different evolutionary strategies in order to acquire novel functionalities, with OC following a gene duplication strategy while MGP variability was obtained mostly by the use of multiple promoters and alternative splicing, leading to proteins with additional functional characteristics and alternative gene regulatory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. The Influence of Therapeutic Radiation on the Patterns of Bone Remodeling in Ovary-Intact and Ovariectomized Mice

    Science.gov (United States)

    Hui, Susanta K; Fairchild, Gregory R; Kidder, Louis S; Sharma, Manju; Bhattacharya, Maryka; Jackson, Scott; Le, Chap; Petryk, Anna; Islam, Mohammad Saiful; Yee, Douglas

    2013-01-01

    Purpose To characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact and ovariectomized mice and evaluate the influence of radiation on the pattern of bone mineral remodeling. Methods Young adult, female BALB/c mice, ovary-intact (I) and ovariectomized (OVX), were used (n=71). All mice were intravenously injection with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were measured. Cellular activity and dynamic histomorphometry were performed. Results Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTX increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the ovary-intact mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R exhibited diminished osteoblasts surface, osteoclast number and mineral apposition rate. Conclusions Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically-relevant, therapeutic radiation exposure. Ovary-intact and ovariectomized murine models have similar 45Ca excretion but different bone microarchitecture responses. 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help identify the appropriate time for clinical intervention to preserve skeletal integrity. PMID:23314741

  10. Changes in bone microarchitecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual.

    Science.gov (United States)

    Vogiatzi, Maria G; Tsay, Jaime; Verdelis, Kostas; Rivella, Stefano; Grady, Robert W; Doty, Stephen; Giardina, Patricia J; Boskey, Adele L

    2010-06-01

    Osteoporosis and fractures occur frequently in patients with beta-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta-chain genes. The heterozygous th3/+ mouse has moderate anemia and serves as a model of beta-thalassemia intermedia, which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) microCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both th3/+ and th3/th3 (P < 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in th3/+ (P < 0.05); (3) microCT abnormalities in th3/+ mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3, and expression of cathepsin K and osteocalcin from bone of both th3/+ and th3/th3 animals was reduced (P < 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both th3/+ and th3/th3 (P < 0.01). In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.

  11. Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.

    Science.gov (United States)

    Inaba, Naoko; Sato, Toshiro; Yamashita, Takatoshi

    2015-01-01

    Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.

  12. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  13. Characterization of a silencer element in the first exon of the human osteocalcin gene.

    Science.gov (United States)

    Li, Y P; Chen, W; Stashenko, P

    1995-01-01

    Osteocalcin, the major non-collagenous protein in bone, is transcribed in osteoblasts at the onset of extracellular matrix mineralization. In this study it was demonstrated that sequences located in the first exon of the human osteocalcin gene possess a differentiation-related osteocalcin silencer element (OSE). Osteocalcin was rendered transcribable in UMR-106 cells and proliferating normal osteoblasts after deletion of the -3 to +51 region. Site-specific mutagenesis of this region revealed that a 7 bp sequence (TGGCCCT) (+29 to +35) is critical for silencing function. Mobility shift assays demonstrated that a nuclear factor bound to the OSE. The OSE binding protein was present in proliferating normal pre-osteoblasts and in UMR-106 and ROS 17/2.8 osteosarcoma cells, but was absent from post-proliferative normal osteoblasts. The binding protein was inhibited by fragments containing the +29/+35 sequence, but not by other promoter fragments or by the consensus oligomers of unrelated nuclear factors AP-1 and Sp1. DNase 1 footprinting demonstrated that the OSE binding-protein protected the +17 to +36 portion of the first exon, consistent with the results of mapping studies and competitive mobility shift assays. It is hypothesized that this silencer is activated by complexing of the OSE binding protein to the OSE during the osteoblast proliferation stage and that the OSE binding protein is down-regulated at the onset of extracellular matrix mineralization. Images PMID:8559666

  14. Ⅰ型神经纤维瘤病伴脊柱侧凸患者骨密度与血清骨钙素和骨代谢生化指标的相关性%The relationship of bone mineral density with osteocalcin and bone metabolism index in scoliosis pa-tients secondary to neurofibromatosis type 1

    Institute of Scientific and Technical Information of China (English)

    朱承跃; 朱泽章; 刘臻; 王守丰; 朱锋; 邱勇

    2014-01-01

    Objectives: To investigate the relationship of bone mineral density (BMD) with osteocalcin (BGP) and serum levels of bone metabolism indexes in scoliosis patients secondary to neurofibromatosis type 1(NF1-S). Methods: From February 2012 to March 2013, 17 NF1-S patients aged 8-18 years old and with the Cobb angle ranging from 40° to 143° were recruited as the case group, while 17 healthy peers ranged 7-19 years old were recruited as the control group. Dual-energy X-ray absorptiometry was used to measure the BMD of two groups. The bone metabolism indexes including BGP, serum alkaline phosphatase (ALP), serum calcium, serum phosphorus, urinary calcium, urinary phosphorus, and urinary creatinine were measured by us-ing electro-chemilumin escence immunoassay and an automatic biochemical analyzer. SPSS 16.0 software was used for data analysis. Independent-sample t test was used to analyze the differences of BMD and bone metabolism indexes between two groups, the relationship between lumbar BMD and bone metabolism was ac-cessed by using Pearson correlation analysis. Results: No difference in terms of age and sex was noted in two groups (P>0.05). The BMD of the lumbar spine and the proximal femur in case group was significantly lower than that of the control group (P serum phosphorus (1.75mmol/L) and urinary calcium/creatinine (U Ca/Cr, 0.10mg/mg) were significantly higher than those of control group(79ng/ml, 2.45mmol/L, 1.47mmol/l, 0.06mg/mg)(P0.05). The factors, including BGP (r=-0.916, P=0.000) and U Ca/Cr (r=-0.968, P=0.000), were both negatively related with lumbar BMD. Conclusions: The BMD in NF1-S patients is significantly lower than those of the normal control. The levels of BGP, serum calcium, serum phosphorus and U Ca/Cr in NF1-S patients are higher than that of the normal control. The level of BGP and U Ca/Cr is a more sensitive index to monitor the situation of BMD in NF1-S patients.%目的:探讨Ⅰ型神经纤维瘤病(neurofibromatosis type 1,NF1)

  15. Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

    Science.gov (United States)

    Joshi, R N; Safadi, F F; Barbe, M F; Del Carpio-Cano, Fe; Popoff, S N; Yingling, V R

    2011-10-01

    Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals' intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of

  16. Changes in bone micro-architecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual

    Science.gov (United States)

    Vogiatzi, Maria G.; Tsay, Jaime; Verdelis, Kostas; Rivella, Stefano; Grady, Robert W; Doty, Stephen; Giardina, Patricia J; Boskey, Adele L

    2010-01-01

    Osteoporosis and fractures occur frequently in patients with beta thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta chain genes. The heterozygote th3/+ mouse has moderate anemia, and serves as a model of beta thalassemia intermedia (TI), which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta thalassemia major (TM), which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls: i) Micro-CT of trabecular bone showed decreased bone volume fraction, number of trabeculae and trabecular thickness in both th3/+ and th3/th3 (p<0.05). ii) Cortical bone analysis showed thinner cortices and increased marrow area in th3/+ animals (p<0.05). iii) Micro-CT abnormalities in th3/+ mice were present by 2 months and did not worsen with age. iv) Histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3. Similarly, cathepsin K and osteocalcin expression from bone of both th3/+and th3/th3 animals was reduced (p<0.05). vi) Biomechanics showed reduced maximum load, maximum moment and structural stiffness in both th3/+and th3/th3 (p<0.01). In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans, and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover, and develop early on during the period of bone accrual. PMID:20449578

  17. Improved surface bioactivity of stainless steel substrates using osteocalcin mimetic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, Samaneh [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Vali, Hojatollah [Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montréal, QC H3A 0C7 (Canada); Faghihi, Shahab, E-mail: sfaghihi@nigeb.ac.ir [Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of)

    2014-02-14

    Although stainless steel has a good biocompatibility for most clinical cases, the higher tissue response (bone bonding property) is required in orthopedic field. In this study, to improve bone-bonding ability of stainless steel substrates, a specific sequence of osteocalcin mimetic peptide is used as bioactive coating material to biochemically modify the surface of metallic samples. This sequence consists of thirteen amino acids present in the first helix of osteocalcin is synthesized in amidic form and physically adsorbed on the surface of 316LS (316 low carbon surgical grade) stainless steel substrates. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to characterize the surface of peptide coated and uncoated substrates. The bioactivity and bone bonding ability of coated and uncoated substrates are assessed by level of hydroxyapatite formation, using transmission electron microscopy (TEM), energy-dispersive x-ray (EDS), and scanning electron microscopy (SEM). The pre-osteoblast cell attachment and proliferation are also evaluated by MTT assay. The results show that the surface of coated sample is homogenously covered by the peptide and display a rougher surface relative to uncoated sample. TEM images reveal the formation of plate-like hydroxyapatite crystals in the presence of the peptide and an amorphous calcium phosphate phase without the peptide. Pre-osteoblast cells proliferation is significantly higher on the surface of peptide coated substrate, while cell attachment remains unaffected by the peptide coatings. Pre-osteoblast cells also demonstrate a higher degree of spreading on the surface of coated sample. It is believed that osteocalcin mimetic peptide improve surface bioactivity and promote hydroxyapatite crystal formation may lead to increased mineralization and bone formation on the surface of metallic biomedical devices. - Graphical abstract: A peptide sequence located in the first helix of OC is selected based on its

  18. Effect of alendronate sodium on serum alkaline phosphatase, osteocalcin and bone mineral density in patients with postmenopausal osteoporosis%阿仑膦酸钠对绝经后骨质疏松症患者骨密度及血清碱性磷酸酶、骨钙素的影响

    Institute of Scientific and Technical Information of China (English)

    白孟海; 白洁; 郑蓉; 陈克明; 刘茗露

    2012-01-01

    目的:探讨阿仑膦酸钠对绝经后骨质疏松症患者骨密度(BMD)及血清碱性磷酸酶(ALP)、骨钙素(BGP)的影响.方法:62例绝经后骨质疏松症患者随机分为2组,治疗组32例,对照组30例.治疗组口服阿仑膦酸钠、阿法迪三;对照组口服阿法迪三.分别于治疗前、治疗6个月、治疗12个月双能X线骨密度仪测定患者正位腰椎(L2~4)、髋部股骨颈(Neck)、大转子(Troch)和Ward’s三角区BMD,全自动生物分析仪测定血清ALP和BGP含量.结果;治疗组治疗6个月、12个月血清ALP和BGP含量与对照组比较有明显差异(P<0.01).治疗组,治疗12个月后L1_4和髋部(Neck,Troch.Ward's)BMD值与治疗前比较显著增加(P<0.01).治疗组与对照组比较L1-4和全髋部BMD值明显差异(P<0.01).结论:阿仑膦酸钠能有效阻止绝经后骨矿丢失,降低血清ALP含量和提高血清BGP含量.%Objective: To investigate the effect of alendronate sodium on serum alkaline phosphatase (ALP), osleocalein and bone mineral density (BMD) in patienis with postmenopausal osteoporosis. Methods,- A iota! Of 62 postmenopausal women with osteoporosis were randomly divided into 2 groups: 32 treatment patients received alendronate sodium and Alpha D3 treatment, and 30 control patients received Alpha D3 only. Before treatment, 6 and 12 months after treatment, the postmenopausal BMD of anterior - posterior lumbar spines and proximal femur were determined by dual - energy X - ray abaorptiometry, and the serum alkaline phosphatase and osteocalein were detected. Results-. Compared with control group, the serum ALP and osteocalcin levels were significantly decreased 6 and 12 months after treatment (P<0.01). Compared with that before treatment, the BMD value of the lumbar spine and proximal femur wag significantly increased 12 months after treatment (P <0.05 ). There was also obvious difference in BMD level of the lumbar spine and proximal femur 12 months afiei treatment between

  19. Milk-derived proteins and minerals alter serum osteocalcin in prepubertal boys after 7 days

    DEFF Research Database (Denmark)

    Mark, A.B.; Hoppe, Camilla; Michaelsen, K.F.

    2010-01-01

    We have previously shown that at equal protein content, milk, but not meat, decreased bone turnover in boys. This suggested that milk-derived components are important for bone metabolism. In the present study, we hypothesized that milk-derived proteins (whey and casein) affect bone turnover during...... growth depending on the content of milk minerals (calcium and phosphorus). This was a randomized, parallel, double-blind study. Eight-year-old boys (n = 57) received 1 of 4 milk drinks: whey protein with low or high content of minerals, or casein protein with low or high content of minerals. The amount...... of whey and casein was identical to their content in 1.5 L of milk. We measured serum osteocalcin (sOC), bone-specific alkaline phosphatase, and C-terminal telopeptides of type 1 collagen (immunoassay) and estimated dietary intake (3-day weighed food record) at baseline and after 7 days. Only s...

  20. In Vivo Determination of Vitamin D Function Using Transgenic Mice Carrying a Human Osteocalcin Luciferase Reporter Gene

    Directory of Open Access Journals (Sweden)

    Tomoko Nakanishi

    2013-01-01

    Full Text Available Vitamin D is an essential factor for ossification, and its deficiency causes rickets. Osteocalcin, which is a noncollagenous protein found in bone matrix and involved in mineralization and calcium ion homeostasis, is one of the major bone morphogenetic markers and is used in the evaluation of osteoblast maturation and osteogenic activation. We established transgenic mouse line expressing luciferase under the control of a 10-kb osteocalcin enhancer/promoter sequence. Using these transgenic mice, we evaluated the active forms of vitamins D2 and D3 for their bone morphogenetic function by in vivo bioluminescence. As the result, strong activity for ossification was observed with 1α,25-hydroxyvitamin D3. Our mouse system can offer a feasible detection method for assessment of osteogenic activity in the development of functional foods and medicines by noninvasive screening.

  1. In vitro and in vivo evaluation of akermanite bioceramics for bone regeneration.

    Science.gov (United States)

    Huang, Yan; Jin, Xiaogang; Zhang, Xiaoling; Sun, Hongli; Tu, Jinwen; Tang, Tingting; Chang, Jiang; Dai, Kerong

    2009-10-01

    This study investigated the effects of a calcium magnesium silicate bioceramic (akermanite) for bone regeneration in vitro and in vivo, with beta-tricalcium phosphate (beta-TCP) as a control. In vitro, the human bone marrow-derived mesenchymal stromal cells (hBMSCs) were cultured in an osteogenic medium supplemented with a certain concentration of two bioceramics' extracts for 20 days. An MTT assay showed that akermanite extract promoted proliferation of hBMSC significantly more than did beta-TCP extract. The results of alkaline phosphatase (ALP) activity test and the expression of osteogenic marker genes such as ALP, osteopontin (OPN), osteocalcin (OCN) and bone sialoprotein (BSP) demonstrated that the osteogenic differentiation of hBMSC was enhanced more by akermanite extract than by beta-TCP extract. In vivo, a histomorphology analysis and histomorphometry of the two porous bioceramics implants in rabbit femur defect models indicated that both in early- and late-stage implantations, akermanite promoted more osteogenesis and biodegradation than did beta-TCP; and in late-stage implantations, the rate of new bone formation was faster in akermanite than in beta-TCP. These results suggest that akermanite might be a potential and attractive bioceramic for tissue engineering.

  2. Therapeutic Effects of Cortex acanthopanacis Aqueous Extract on Bone Metabolism of Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Zhiguo Zhang

    2012-01-01

    Full Text Available The aim of this study was to evaluate effects of aqueous extract from Cortex acanthopanacis (CAE on osteoporosis rats induced by ovariectomy (OVX using aqueous extract from Folium Epimedii (FEE as positive control agent. Three-month-old female rats that underwent OVX were treated with CAE. After 12 weeks, bone mineral density (BMD and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG and receptor activator of nuclear factor kappa-B ligand (RANKL in tibia were evaluated. In addition, the serum concentrations of osteocalcin (OC, interleukin-1 beta (IL-1β, interleukin-6 (IL-6, calcitonin (CT, and parathyroid hormone (PTH were determined. Administration of CAE significantly prevented OVX-induced rats from gain of the body weight. Treatment with CAE increased bone mass remarkably and showed a significant inhibitory effect on bone resorption by downregulating significantly the expression of RANKL in tibia of OVX rats. Meanwhile, treatment of CAE significantly reduced serum level of IL-1β and increased level of CT in OVX rats. This suggests that CAE has the potential to be used as an alternative therapeutic agent for postmenopausal osteoporosis.

  3. 24 hr Whole-Body Retension of {sup 99m}Tc-Methylene Diphosphonate and Osteocalcin in patients with Hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Yeoum, Kwang Seop; Lee, Jin Oh; Kang, Tae Woong; Lim, Sang Moo; Hong, Sung Woon [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1990-07-15

    The development of histomorphometric and histodynamic investigations has permitted the description of a specific and complex osteopathy in hyperthyroidism. The increased bone turnover rate in hyperthyroid patients may be accompanied by a considerable bone loss. These features are associated with both increased osteoclastic bone resorption and increased osteoclastic bone formation, with an accelerated calcification rate. Conventional biochemical markers of bone metabolism, i.e. serum calcium and alkaline phosphatase and urinary hydroxyproline and calcium are normal in most patients with hyperthyroidism. However, the correlation between serum BGP and serum concentration of thyroid hormon suggests that serum BGP may be a sensitive marker of increased bone formation due to the hypersecretion of thyroid hormones. Any increase in bone turnover, whether focal or diffuse, will result in an increase in {sup 99m}Tc-methylenediphosphonate uptake (MDP). The measurement of this uptake in hyperthyroid patients by bone provides a sensitive and objective means of quantifying skeletal metabolism. Using a standard shadow-shield whole-body monitor and radioimmunoassay kit, we have measured whole-body retention of {sup 99m}Tc-MDP up to 24 hr and concentration of serum Osteocalcin in 20 patients with hyperthyroidism and in 42 normals. The results were as follows; 1) The average of serum Osteocalcin level in 42 patients with normals was 9.90 +- 4.87(ng/ml) and in 20 patients with hyperthyroidism was 19.54 +- 5.7(ng/ml). Both the averages of serum Osteocalcin and 24 hr {sup 99m}Tc-MDP uptakes in hyperthyroid patients were higher than those in normals. 2) {sup 99m}Tc-MDP uptakes in skeletal system increased in proportion to normal ageing after 40 yrs old in 42 patients with normals. The average of {sup 99m}Tc-MDP uptakes in hyperthyroid patients were higher than those in normals without related ageing. 3) A significant relationships between the {sup 99m}Tc-MDP uptakes and serum

  4. Ectopic expression of telomerase enhances osteopontin and osteocalcin expression during osteogenic differentiation of human mesenchymal stem cells from elder donors

    Directory of Open Access Journals (Sweden)

    Machado CB

    2009-01-01

    Full Text Available Age related bone loss is one of the most prevalent diseases in the elder population. The osteoblasts are the effectors cells of bone formation and regeneration. With the aging the osteoblasts become senescent reducing their ability to produce bone. Cellular replicative senescence is triggered by telomers shortening. Telomerase elongate the telomers length and maintain the cell proliferative capacity. Here, we demonstrated that the expression of human telomerase reverse transcriptase mediated by an adenovirus vector increases the levels of osteopontin and osteocalcin mRNA during the in vitro osteogenic differentiation of elderly human mesenchymal stem cells. Bone marrow human mesenchymal stem cells were obtained from old donors (>65 years and induced to differentiate into osteoblasts for 14 days. The levels of mRNA of human telomerase reverse transcriptase, osteopontin and osteocalcin during the differentiation were assessed by semi-quantitative PCR before and during the differentiation on days 7 and 14. Infected cells showed 1.5 fold increase in telomerase expression. Also telomerized cells exhibit 1.5 fold increase in osteopontin and 0.5 fold increase in osteocalcin expression compared to primary osteoblasts isolated from the same donors. The transformed cells were not able to form tumours in NUDE mice.

  5. 骨碱性磷酸酶 N-端骨钙素99Tcm-亚甲基二膦酸盐骨显像与早期骨代谢改变%The change of bone alkaline phosphatase,N-osteocalcin and 99Tcm-MDP bone imaging on bone metabolism in early stage

    Institute of Scientific and Technical Information of China (English)

    罗裕旋; 吴传安; 杨伟康; 何小媚; 魏建伟; 梁瑞金; 余树林

    2015-01-01

    目的:探讨骨碱性磷酸酶(BALP)、N-端骨钙素(BGP)、99 Tc m-亚甲基二膦酸盐(MDP)骨显像与早期骨代谢改变的关系。方法通过注射地塞米松磷酸钠针剂(DX)得到骨质疏松兔,注射时间为6周。将兔分为3组,正常对照组、骨质疏松对照组(DX 注射量为2 mg/kg,1周2次)、骨量减少组(DX 注射量为1 mg/kg,1周1次)。分别检测3组的核素99 Tc m-MDP 骨显像、病理切片骨组织学、骨密度以及血清 BALP 与 BGP。对第3腰椎、膝关节、股骨头、股骨中段以及第4尾椎进行感兴区(ROI)半定量检测作比较。结果骨质疏松对照组与骨量减少组相比,在核素骨显像中只有股骨中段对99 Tc m-MDP 摄取的 ROI 比值上升(P 0.05);但骨密度以及血清 BALP 差异具有统计学意义(P 0.05).But the bone density and serum BALP results showed significant difference (P <0.05).Conclusion 9 9 Tc m-MDP bone imaging showed,the ROI ratio of femoral head,third lumbar,knee joint and fourth tail verte-brae ROI are increased.The ROI ratio in the middle part of the femur is not increased,it might be the time of bone mass reduction,the BGP support conclusion is more meaningful,and can provide reference for early preven-tion and treatment.

  6. Effectiveness of tissue engineered chitosan-gelatin composite scaffold loaded with human platelet gel in regeneration of critical sized radial bone defect in rat.

    Science.gov (United States)

    Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali; Kamali, Amir

    2017-03-29

    Although many strategies have been utilized to accelerate bone regeneration, an appropriate treatment strategy to regenerate a new bone with optimum morphology and mechanical properties has not been invented as yet. This study investigated the healing potential of a composite scaffold consisting of chitosan (CS), gelatin (Gel) and platelet gel (PG), named CS-Gel-PG, on a bilateral critical sized radial bone defect in rat. Eighty radial bone defects were bilaterally created in 40 Sprague-Dawley rats and were randomly divided into eight groups including untreated, autograft, CS, Gel, CS-PG, Gel-PG, CS-Gel, and CS-Gel-PG treated defects. The bone defects were evaluated clinically and radiologically during the study and their bone samples were assessed by gross and histopathology, histomorphometry, CT-scan, scanning electron microscopy, and biomechanical testing after 8weeks of bone injury. The autograft and CS-Gel-PG groups showed significantly higher new bone formation, density of osseous and cartilaginous tissues, bone volume, and mechanical performance than the defect, CS and Gel-PG groups (P˂0.05). In addition, bone volume, density of osseous and cartilaginous tissues, and numbers of osteons in the CS-Gel-PG group were significantly superior to the CS-PG, CS-Gel and Gel groups (P˂0.05). Increased mRNA levels of alkaline phosphatase, runt-related transcription factor 2, osteocalcin, collagen type 1 and CD31, vascular endothelial growth factor as osteogenic and angiogenic differentiation markers were found with the CS-Gel-PG scaffold by quantitative real-time PCR in vitro after 30days of culturing on bone marrow-derived mesenchymal stem cells. In conclusion, the healing potential of CS-Gel scaffold embedded with PG was comparable to autografting and therefore, it can be offered as an appropriate scaffold in bone tissue engineering and regenerative applications.

  7. Osteoinductive active material complex with Platelet-rich fibrin guide the new bone formation on extraction sites by bone histomorphometry%骨诱导活性材料复合富血小板纤维蛋白在拔牙位点引导新骨形成的骨计量学研究

    Institute of Scientific and Technical Information of China (English)

    周春梅; 温齐古丽·乃库力; 于莉; 袁萍; 尼加提·吐尔逊

    2016-01-01

    Objective:The aim of the study was to explore study the effect that osteoinductive active material(OAM) combined with platelet-rich fibrin (PRF) lead to the formation of new bone in the extraction site,and to investigate the re-sult that the composite promoted the preservation and restoration of extraction site. Method:The 12-month-old male Beagle dogs with the number of six were extracted both second maxillary and mandibular lateral incisors with the minimally extract-ed method. To establish the animal model,the four sites were randomly divided into four groups,as A,B,C and D. The for-mer three groups were filled with OAM-PRF composite,OAM and PRF respectively,and D controlled group. Three dogs were randomly sacrificed after one-month treatment,and the left three dogs were sacrificed after three-month treatment. The samples were taken from the alveolar bone and as followed stained with toluidine blue and H.E respectively for histomorpho-metric observation. Result:The trabecular width,trabeculae area and an osteoblastic number of group A are significantly higher than the other three groups(P<0.01). The factorial analysis shows the effect of the OAM-PRF complex is superior to use OAM or PRF alone,guiding the new bone formation in the extraction site area. Conclusion:The number of osteoblasts can increase significantly under the effect of OMA complex with PRF,which contribute to bone remodeling and improving the quality of alveolar bone in tooth extraction site.%目的:研究骨诱导活性材料(Osteoinduction Active Material,OAM)复合富血小板纤维蛋白(Platelet-rich Fibrin,PRF)在拔牙位点引导新骨形成的作用,考察OAM复合PRF促进拔牙位点保存修复的效果。方法:选取12月龄健康雄性Beagle犬6只,建立动物模型,微创拔除两侧上、下颌第二侧切牙。4个位点随机分为A、B、C、D 4组,分别植入PRF与OAM复合物、单一的PRF或OAM,以及空白对照。术后1个月和3

  8. Serum osteocalcin is associated with dietary vitamin D, body weight and serum magnesium in postmenopausal women with and without significant coronary artery disease.

    Science.gov (United States)

    Alissa, Eman M; Alnahdi, Wafa A; Alama, Nabeel; Ferns, Gordon A

    2014-01-01

    Osteoporosis and atherosclerosis often present atypically in postmenopausal women, making clinical recognition difficult. Prospective studies suggest independent associations between bone mass and vascular calcification through vitamin D deficiency as an established predictor of both conditions. We aimed to examine the relationship between serum osteocalcin and vitamin D status in postmenopausal women with and without angiographic evidence of coronary artery disease (CAD). One hundred and eighty postmenopausal women undergoing coronary angiography were selected sequentially from the Catheterization unit of King Abdulaziz University Hospital. Socio-demographic, anthropometric parameters and dietary habits were measured. Biochemical variables were estimated in blood samples. Half of the postmenopausal women did not have significant CAD, 24% had significant CAD in a single and/or double coronary vessels, 26% had significant CAD in three coronary vessels. Mean serum vitamin D concentrations showed that vitamin D deficiency was a common finding in the whole population. Vitamin D and calcium intakes were uniformly low in the study cohort. Serum osteocalcin was significantly correlated with dietary vitamin D in all subgroups (r=-0.172, pmagnesium, alkaline phosphatase, dietary vitamin D, and body weight were independent variables of serum osteocalcin level. In conclusion, elevated levels of serum C reactive protein and vitamin D were associated with low serum osteocalcin levels. Therefore, osteocalcin may be a potential cardiovascular risk marker. However, further studies are needed to clarify the pathophysiological processes underlying the relationship between serum osteocalcin level and atherosclerosis parameters.

  9. Osteopontin, osteocalcin, and osteoprotegerin expression in human tissue affected by cleft lip and palate

    Directory of Open Access Journals (Sweden)

    Smane L.

    2016-01-01

    Full Text Available Cleft lip and palate (CLP is a common congenital anomaly with a complex etiology which has not been elucidated yet. This study investigated whether expression of osteopontin (OPN, osteoprotegerin (OPG, and osteocalcin (OC, which are essential for the normal craniofacial bone remodelling, is not regulated in children with CLP. Alveolar bone tissue samples were obtained from patients with complete bilateral (CB CLP (n = 14 during corrective plastic surgery and unaffected control subjects (n = 9. OPN, OPG, and OC expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. OPN expression was observed only sporadically in the alveolar bone of 3 patients, in contrast to the control group (z = −2.962; P < 0.003. The number of OPG-positive bone cells varied from occasional to moderate, in contrast to the control group (z = −2.247; P = 0.025. OC-positive osteocytes were present in moderate to numerous numbers in both patients and controls, with no significant difference between them (z = −1.356; P < 0.175. The prominent expression of OC characteristic for CBCLP affected hard tissue indicates a high potential of bone mineralization. Few OPG-positive osteocytes in the bone tissue implicate the disregulation of osteoclast differentiation, maturation, and activity, but few OPN-containing cells may prove the common disregulation of bone remodelling during cleft morphopathogenesis.

  10. Skeletal growth after oral administration of demineralized bone matrix.

    Science.gov (United States)

    Martínez, J A; Elorriaga, M; Marquínez, M; Larralde, J

    1993-03-01

    Oral administration of bone extracts obtained from bovine demineralized bone matrix to rats has a direct effect on bone metabolism, affecting bone proportions and some markers of bone formation such as bone malate dehydrogenase, serum alkaline phosphatase and serum osteocalcin. Furthermore collagen deposition, bone protein synthesis and nucleic acids content were significantly increased by the treatment.

  11. Comparison of urinary excretion of Deoxypiridinoline and value of serum Osteocalcin within the Knee Osteoarthritis grading

    Directory of Open Access Journals (Sweden)

    Harry Isbagio

    2004-06-01

    Full Text Available The identification of molecular markers, which reflects differences in disease progression rates in Osteoarthritis (OA, would greatly facilitate clinical studies. Urinary Deoxypyridinoline (UDPD and serum osteocalcin (OC had been widely used for marker of bone metabolism, but the use for molecular marker in OA was lack of data. Recent studies show that there were conflicted results between urinary excretion of DPD and serum OC value within knee OA grading. The aim of this study is to compare of urinary excretion of DPD and the level of serum OC as destructive parameter of cartilage within the knee OA grading. This cross sectional study comprise of 69 patients with OA of knee joints. Kellgren and Lawrence scale was use for grading of OA. Group of patients with knee OA grade 2 call as group of early OA and group of patients with knee OA grade 3 and 4 calls as group of late OA. DPD in urine was measured using Immuno-chemilunescence, serum osteocalcin was measured using Elisa method. The mean value of urinary concentrations of DPD in OA patients was higher than normal value (9.79 ± 7.28 nM DPD/mM Creatinin, and the mean value of serum OC within normal value (8.49 ± 4.68 ng/mL. There were no significant differences of age, body mass index (BMI, duration of illness, urinary excretion of UDPD and serum OC level between early and late OA. In conclusion, there is no significant difference of urinary excretion of DPD and serum OC level within knee OA grading. The use of urinary DPD and serum OC as molecular markers of progression of OA needed to be explored by other longitudinal study. (Med J Indones 2004; 13: 96-101 Keywords: Knee osteoarthritis, deoxypiridinoline, osteocalcin

  12. Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats.

    Science.gov (United States)

    Haffa, A; Krueger, D; Bruner, J; Engelke, J; Gundberg, C; Akhter, M; Binkley, N

    2000-05-01

    To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K (phylloquinone [K1], 20 microg/kg diet), control K (K1, 1300 microg/kg diet), low-dose W (W, 1.5 mg/kg control diet), or high-dose W plus K (W/K1, 10/100 mg/kg diet). Femur bone mineral content (BMC) and bone mineral density (BMD), plasma prothrombin time (PT) and prothrombin concentration (PC), and serum total alkaline phosphatase (ALP) and skeletal alkaline phosphatase (sALP) were measured at baseline and days 20, 40, 60, and 80. Serum total osteocalcin (OC) and undercarboxylated osteocalcin (ucOC) and femur length (FL) were measured at baseline and day 80. Left femur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circulating ucOC (17% higher than control; p diet manipulation. This does not hinder peak bone mass attainment in female rats; however, W causes less newly synthesized OC to be deposited in bone.

  13. Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate

    Energy Technology Data Exchange (ETDEWEB)

    Reeve, J.; Arlot, M.; Wootton, R.; Edouard, C.; Tellez, M.; Hesp, R.; Green, J.R.; Meunier, P.J.

    1988-06-01

    In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using /sup 18/F) and bone turnover (using /sup 85/Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by /sup 18/F correlated with an index of /sup 85/Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group.

  14. Evidence for the formation of a complex between osteopontin and osteocalcin.

    Science.gov (United States)

    Ritter, N M; Farach-Carson, M C; Butler, W T

    1992-08-01

    We hypothesize that the mechanisms governing bone formation and remodeling involve the assembly of some of the components of the extracellular matrix into supramolecular complexes. We have examined the associations of osteopontin (OPN) with other proteins isolated from demineralized rat long bones. Three ligand binding techniques were used to demonstrate the formation of complexes between osteopontin and osteocalcin (OCN). Using gel overlay assays, the binding between soluble 125I-OPN and OCN immobilized in acrylamide gels was visualized. Competition for 125I-OPN-OCN complexes was demonstrated when unlabeled OCN-enriched bone extract was included in gel overlay solutions. Also, gel overlay assays showed 125I-OCN binding to OPN. Saturable binding was shown in solid-phase filter binding assays, which yielded an equilibrium binding constant of moderately high affinity (approximately 10(-8) M). Specificity of OPN-OCN complex formation was confirmed by measuring binding in the presence of unlabeled OPN and OCN versus a bone-localized serum protein, alpha 2HS-glycoprotein. Finally, the formation of soluble complexes were demonstrated in a modified Hummel-Dreyer gel filtration assay. These results indicate that OPN and OCN form complexes in vitro. The possible functions of OPN-OCN complexes in osteoclast recruitment and attachment are discussed.

  15. Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway.

    Science.gov (United States)

    Dong, Meng; Jiao, Guangjun; Liu, Haichun; Wu, Wenliang; Li, Shangzhi; Wang, Qingshi; Xu, Daxia; Li, Xiaofeng; Liu, Huan; Chen, Yunzhen

    2016-10-01

    Silicon is essential for bone formation. A low-silicon diet leads to bone defects, and numerous animal models have demonstrated that silicon supplementation increases bone mineral density (BMD) and reduces bone fragility. However, the exact mechanism of this action has not been characterized. In this study, we aimed to determine the role of biological silicon in the induction of osteoblast differentiation and the possible underlying mechanism. We examined whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related transcription factor 2 (RUNX2) signaling pathway by investigating its effect in vitro at several concentrations on COL-1 and osteocalcin synthesis in human osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins was detected by Western blotting following exposure to noggin, an inhibitor of BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2. Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 μM orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2, COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the formation of mineralized nodules were also observed under these conditions. Furthermore, preconditioning with noggin inhibited the silicon-induced upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP-2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic differentiation of rat BMSCs.

  16. Effect of osteocalcin on metabolism of gluose and lipid%骨钙素对糖、脂代谢影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    王计艳

    2011-01-01

    Osteocalcin, particularly from mature osteoblasts, is a useful marker of bone turn over and bone formation. Recently, animal and cell studies have suggested that the skeleton acts as an endocrine organ through secreting osteocalcin, which plays a role in glucose and fat metabolism. It had been shown that incomplete carboxyladon of osteocalcin can increase pancreatic β-cell proliferation and insulin secretion while complete carboxylation of osteocalcin can improve insulin sensitivity. Moreover, research demonstrated that fat metabolism interacts with skeleton metabolism via adiponectin.%成骨细胞分泌的骨钙素是骨形成和骨转换的标志,但最近的动物及细胞试验均证实骨骼可以视为一个内分泌器官,它通过分泌骨钙素来影响糖和脂的代谢.羧化不全骨钙素可以促进胰岛B细胞增殖与胰岛素分泌,而羧化完全骨钙素可以提高胰岛素的敏感性.同时,实验还证实脂肪代谢和骨代谢与脂联素关系密切.

  17. Young overweight and obese women with lower circulating osteocalcin concentrations exhibit higher insulin resistance and concentrations of C-reactive protein.

    Science.gov (United States)

    Lucey, Alice J; Paschos, Georgios K; Thorsdottir, Inga; Martínéz, J Alfredo; Cashman, Kevin D; Kiely, Máireád

    2013-01-01

    The role of the skeleton in the regulation of energy metabolism in humans is not clear. This study investigates the hypothesis that biomarkers of bone turnover are associated with indices of glucose homeostasis and systemic inflammation in young adults. A cross-sectional study investigating the relationships between biomarkers of bone turnover (serum total and uncarboxylated osteocalcin, bone-specific alkaline phosphatase, C-telopeptide of type I collagen, urinary N-telopeptide of type I collagen) and glucose metabolism (fasting plasma glucose [FPG], insulin, insulin resistance [homeostatic model assessment of insulin resistance]), systemic inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6), adipokines (leptin and adiponectin), and body composition was conducted in 268 young, nondiabetic overweight and obese adults aged 20 to 40 years (116 men, 152 women; body mass index, 27.5-32.5 kg/m(2)). Data on diet, physical activity, serum 25-hydroxyvitamin D, and parathyroid hormone were also collected. In women, there was a stepwise increase in lean body mass (P insulin resistance (β = -0.508; P = .001; 95% CI, -10.93 to -3.17) in women with total osteocalcin concentrations below the group median. Men in the lowest tertile of uncarboxylated osteocalcin had twice the concentration of hsCRP than did other men (P = .05). In this sample, women with less lean body mass had lower circulating total osteocalcin concentrations and exhibited higher FPG, insulin resistance, and hsCRP compared with their similarly sized counterparts, suggesting that associations between osteocalcin and systemic inflammation, glucose homeostasis, and insulin resistance may be influenced by differences in sex and body composition.

  18. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  19. Mouse adipose tissue-derived adult stem cells expressed osteogenic specific transcripts of osteocalcin and parathyroid hormone receptor during osteogenesis.

    Science.gov (United States)

    Teotia, P K; Hussein, K E-D; Park, K-M; Hong, S-H; Park, S-M; Park, I-C; Yang, S-R; Woo, H-M

    2013-10-01

    Adult mesenchymal stem cells (MSCs) have potential to differentiate into various lineages, replacing cells during normal turnover and tissue regeneration to replace damaged or lost adult tissues during osteoporosis and arthritis, or traumatic injuries. We investigated the osteogenic signature in mouse adipose tissue (AD)- and bone marrow (BM)-derived MSCs. MSCs from adipose tissue and bone marrow were compared for osteogenic endogenous mRNA markers by reverse-transcription polymerase chain reaction (RT-PCR). Cellular proliferation and immunophenotype analyzed by flow cytometry revealed that mouse AD-MSCs and BM-MSCs shared similar characteristics. Isolated AD-MSC and BM-MSC showed high proliferation rates and fibroblast morphology. Flow cytometry revealed positive markers for mesenchyme, but negative for primitive hematopoietic and endothelial cells. At day 21, Alizarin red S and Von-kossa staining of differentiated cells showed high calcium deposits compared with undifferentiated cells. After 21 days of osteogenic differentiation, AD-MSCs expressed osteocalcin and parathyroid hormone (PTH) compared with undifferentiated cells. Osteogenic-specific transcript of osteocalcin (OC), bone gamma carboxyglutamate protein, and PTH receptor (PTHr) were detected only in differentiated not undifferentiated cells. Undifferentiated BM-MSCs, expressed all markers at low intensity, which amplified during differentiation. Our findings suggest that the OC and PTHr can be used as differentiation markers for osteogenesis of mouse AD-MSC. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Analysis of the Influence of Hormone Replacement Therapy on Osteocalcin Gene Expression in Postmenopausal Women.

    Science.gov (United States)

    Rahnama, Mansur; Jastrzębska-Jamrogiewicz, Izabela; Jamrogiewicz, Rafał; Trybek, Grzegorz

    2015-01-01

    Osteocalcin (OC) contributes to the process of bone mineralization. Present study was designed to investigate the changes in OC gene expression of postmenopausal women treated with hormone replacement therapy (HRT). Study was also designed to evaluate OC gene expression in cells which are not part of connective tissue. Research was carried out on 30 postmenopausal women not treated and 30 treated with HRT. Examination of OC gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Densitometry was conducted on femur and mandible. Tests revealed OC gene expression in BEL and PBL. BMD was higher in groups treated with HRT. Assessment of correlation between the OC gene expression in BEL and BMD of mandible revealed significant positive relation. OC gene expression can be stated BEL and PBL. Analysis of correlation between OC gene expression in oral cavity and mandible BMD showed significant correlation between local OC expression and local bone metabolism. The relation between OC gene expression and bone metabolism is complex and further research is needed to clear all of the uncertainties.

  1. Bone histomorphometry of broilers submitted to different phosphorus sources in growing and finisher rations Histomorfometria óssea de frangos de corte submetidos a diferentes fontes de fósforo nas rações de crescimento e terminação

    Directory of Open Access Journals (Sweden)

    Rafael Carvalho de Oliveira

    2006-10-01

    Full Text Available The objective of this work was to identify alterations in the histomorphology of the cortical bone tissue of broilers submitted to growing and finisher rations formulated with five different sources of phosphorus: dicalcium phosphate, simple superphosphate, triple superphosphate, monoammonium phosphate and Araxá rock phosphate. Histological images had their components segmented, and were called regions of interest (ROI. Images were analyzed through developed algorithms, using the SCILAB mathematical environment. Eleven features were considered in order to obtain a complete description of the bone images: percentage of bone by area, ROI area, ROI perimeters, ROI elongation, ROI angle and their respective standard deviations, besides entropy of ROI angles and a texture-oriented measure (lacunarity. The substitution of dicalcium phosphate in growing and finisher rations for any other tested source of phosphorus caused significant changes on the hystomorphology of the cortical broilers bones, for example: diminution of bone percentage by area, increase of lacuna area and worse matrix homogeneity. Changes were more pronounced in the Araxá rock phosphate treatments, with the highest fluorine content, than in simple superphosphate, triple superphosphate and monoammonium phosphate treatments, which were similar.O objetivo deste trabalho foi avaliar alterações histomorfológicas na região do osso cortical de frangos de corte alimentados, nas fases de crescimento e engorda, com rações contendo cinco diferentes fontes de fósforo - fosfato dicálcico, superfosfato simples, superfosfato triplo, fosfato monoamônio e fosfato de rocha de Araxá. Imagens histológicas foram digitalizadas, segmentadas em regiões de interesse (ROI e analisadas por meio de algoritmos desenvolvidos no ambiente de programação SCILAB. Consideraram-se onze características para descrição das imagens: porcentagem de osso por área, área da ROI, perímetro da ROI

  2. The Effect of Estrogen on the Restoration of Bone Mass and Bone Quality in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), shamoperated (Sham-O) and OVX plus estrogen (OVX+E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the structure disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results damonstrated that estrogen treatment increased bone mass and the amount of trabecula by 129% and 132% respectively (P<0. 05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203 %. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics.

  3. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice.

    Science.gov (United States)

    Ferron, Mathieu; McKee, Marc D; Levine, Robert L; Ducy, Patricia; Karsenty, Gérard

    2012-02-01

    The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes.

  4. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  5. 骨钙素:一种重要的能量代谢调节激素%Osteocalcin:an important hormone that regulates energy metabolism

    Institute of Scientific and Technical Information of China (English)

    郭晓强

    2011-01-01

    Osteocalcin is a structure protein synthesized by osteoblasts. This protein becomes carboxylated through post-translation processing and plays roles in skeleton development. But the latest researches have indicated that uncarboxylated osteocalcin can promote the proliferation of pancreas β cell, increase the secretion of insulin, upregulate the expression of adiponectin, weaken insulin resistance and play inhibitory roles in the development of diabetes and obesity. Clinical examinations have indicated the content of osteocalcin is negatively correlated to fasting blood glucose level and insulin concentration. The content of osteocalcin is significantly lower in diabetic patients. These findings suggested that osteocalcin is a hormone that regulates energy metabolism, which deepens the understanding of function of bone and provides a novel target for the treatment of metabolism-related diseases.%骨钙素是一种由成骨细胞合成的结构蛋白,经过翻译后加工生成羟化骨钙素而参与骨骼发育.然而,最新研究发现,未发生羟化修饰的骨钙素可促进胰腺β细胞增殖和胰岛素分泌,增加脂联素基因表达和减弱胰岛素抵抗,对糖尿病和肥胖的发生具有抑制作用.临床检测也发现骨钙素含量与空腹血糖和胰岛素浓度呈负相关,糖尿病患者体内含量明显较低.这些研究确立了骨钙素是一种能量代谢调节的重要激素,拓展了对骨骼功能理解的同时也为治疗代谢性紊乱疾病提供了新靶点.

  6. Osteocalcin is not a strong determinant of serum testosterone and sperm count in men from infertile couples.

    Science.gov (United States)

    Schwetz, V; Gumpold, R; Graupp, M; Hacker, N; Schweighofer, N; Trummer, O; Pieber, T R; Ballon, M; Lerchbaum, E; Obermayer-Pietsch, B

    2013-07-01

    Osteocalcin (OC) - released by osteoblasts and known as a marker of bone turnover - has been suggested to influence male fertility in murine models by enhancing testosterone production and sperm count. Results from clinical studies are scarce, however. The aim of this cross-sectional study was to investigate the proposed association of OC, undercarboxylated osteocalcin (ucOC) or carboxylated osteocalcin (cOC) with testosterone and sperm count in a cohort of 159 young male adults from infertile couples. Semen analysis was performed. Testosterone, free testosterone, LH, OC and ucOC were measured in serum samples after an overnight fast. cOC and OC correlated weakly but significantly with testosterone (OC: r = 0.165, p = 0.040, cOC: r = 0.193, p = 0.017), but not after adjusting for age and body mass index (BMI) or waist-hip ratio (WHR). %ucOC (ucOC levels expressed as percentage of total OC) correlated inversely with LH (r = -0.184, p = 0.023) and remained significant after the same adjustment. No significant correlations were observed between OC, cOC, ucOC, %ucOC and sperm count, semen volume and number of vital spermatozoa. In binary logistic regression analyses, none of the parameters of OC were predictors of oligozoospermia after adjusting for age and BMI or WHR. The weak association between %ucOC and LH has marginal clinical importance because of the lack of associations of parameters of OC with testosterone and sperm count. The current data thus cannot support the notion that OC is associated with male fertility in young men from infertile couples. © 2013 American Society of Andrology and European Academy of Andrology.

  7. Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

    NARCIS (Netherlands)

    Bravenboer, N; Holzmann, PJ; ter Maaten, JC; Stuurman, LM; Roos, JC; Lips, P

    2005-01-01

    Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. Introduction: Adults with growth hormone (GH) deficiency have

  8. Osteoarthritic versus osteoporotic bone and intra‐skeletal variations in normal bone: Evaluation with µCT and bone histomorphometry

    National Research Council Canada - National Science Library

    Zupan, Janja; van't Hof, Rob J; Vindišar, Franci; Haring, Gregor; Trebše, Rihard; Komadina, Radko; Marc, Janja

    2013-01-01

    ...) and microcomputed tomography (µCT) as well as DXA in order to first, test the differences between OA and OP comparing both groups to healthy controls, second, to assess variations between three different skeletal sites in controls...

  9. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, Niels; Brixen, Kim; Eriksen, Erik Fink

    2004-01-01

    -terminal (PINP) propeptides of procollagen I, bone-specific alkaline phosphatase, and osteocalcin were measured to estimate bone formation. Dual energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) of the lumbar spine, hip, and whole body. Serum and urine samples were collected every...

  10. Cancellous bone structure of iliac crest biopsies following 370 days of head-down bed rest

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Morukov, Boris V.; Vico, Laurence

    2005-01-01

    INTRODUCTION: Static bone histomorphometry was applied to existing iliac bone sections originating from a 370-d 5 degrees head-down bed rest experiment. This bed rest experiment is the longest ever to have been conducted. We hypothesized that bed rest would decrease cancellous bone volume fractio...

  11. A change of osteocalcin (OC) and tartrate resistant acid phosphatase 5b (TRACP-5b) with the menstrual cycle.

    Science.gov (United States)

    Lee, S; Kumagai, T; Hashimoto, J; Satoh, A; Suzuki, T; Yamai, K; Ohta, S

    2012-09-01

    Bone metabolism markers associated with 4 menstrual cycle phases were evaluated in 14 healthy young females without menstrual disorder. Menstrual cycle phases were confirmed with basal body temperature for 3 months, luteinizing hormone kits, and sexual hormone concentrations of serum. The bone metabolism markers used were osteocalcin (OC), which was measured by immunoradiometric assay (IRMA), and tartrate resistant acid phosphatase 5b (TRACP-5b), which was measured by enzyme immunometric assay (EIA). The highest values of OC and TRACP-5b were observed in the ovulation phase, and TRACP-5b increased significantly when compared with levels in the menstrual phase (pchanges in sex-hormone secretion involved in OC and TRACP-5b showed specific patterns during the menstrual cycle. In other words, TRACP-5b levels are influenced by sex hormones produced during the menstrual period and are based on the bone-formation status. Therefore, it is presumed that the TRACP-5b levels during ovulation play a central role in bone formation and bone metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Bone Mineral Density, Bone Turnover Markers and Fractures in Patients with Systemic Sclerosis: A Case Control Study: e66991

    National Research Council Canada - National Science Library

    Marco Atteritano; Stefania Sorbara; Gianluca Bagnato; Giovanni Miceli; Donatella Sangari; Salvatore Morgante; Elisa Visalli; Gianfilippo Bagnato

    2013-01-01

    .... BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline...

  13. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study

    National Research Council Canada - National Science Library

    Atteritano, Marco; Sorbara, Stefania; Bagnato, Gianluca; Miceli, Giovanni; Sangari, Donatella; Morgante, Salvatore; Visalli, Elisa; Bagnato, Gianfilippo

    2013-01-01

    .... BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline...

  14. Total and carboxylated osteocalcin associate with insulin levels in young adults born with normal or very low birth weight.

    Directory of Open Access Journals (Sweden)

    Päivi M Paldánius

    Full Text Available OBJECTIVE: Osteocalcin (OC, a bone-derived protein, has been implicated in the regulation of glucose and energy metabolism. Young adults born with very low birth weight (VLBW have altered glucose regulation and lower bone mineral density (BMD compared with those born at term. The aim of this study was to explore the association between bone and glucose metabolism in healthy young adults born prematurely or at term. METHODS: The cohort of this cross-sectional study comprised 332 non-diabetic young adults (age 18 to 27 years born either preterm with VLBW (n = 163 or at term (n = 169. OC, carboxylated osteocalcin (cOC and markers of glucose metabolism were measured at fasting and after a 75-g oral glucose tolerance test (OGTT. RESULTS: VLBW adults were shorter, had lower BMD (p<0.001 and higher fasting OC (p = 0.027 and cOC (p = 0.005 than term-born subjects. They also had higher 2-hour insulin (p = 0.001 and glucose (p = 0.037 concentrations. OGTT induced a significant reduction in OC (p<0.001, similar in both groups. OC reduction was not associated with OGTT-induced increases in insulin (p = 0.54. However, fasting total OC and cOC correlated negatively with fasting insulin after adjustment for age, gender, BMD and VLBW status (r = -0.182, p = 0.009 and r = -0.283, p<0.001, respectively. CONCLUSION: Adults born with VLBW have higher OC and cOC than their peers born at term. This may in part reflect the mechanisms that underlie their lower BMD and decreased insulin sensitivity. Serum OC appears to be negatively associated with long-term glucose regulation whereas acute changes during OGTT may be mediated via other mechanisms.

  15. Osteocalcin induces release of glucagon-like peptide-1 and thereby stimulates insulin secretion in mice.

    Directory of Open Access Journals (Sweden)

    Akiko Mizokami

    Full Text Available The uncarboxylated form (ucOC, but not the γ-carboxylated form (GlaOC, of the bone-derived protein osteocalcin stimulates insulin secretion and regulates energy metabolism in insulin target tissues. Glucagon-like peptide-1 (GLP-1 is an insulin secretagogue that is released from the gut in response to food intake. We have now found that Gprc6a, a putative ucOC receptor, is expressed in epithelial cells of the mouse small intestine as well as in STC-1 enteroendocrine cells. Secretion of GLP-1 by STC-1 cells was stimulated by ucOC but not by GlaOC. The serum GLP-1 concentration in mice was increased by intraperitoneal or oral administration of ucOC, whereas GlaOC was effective in this regard only after oral application. Serum insulin levels were also increased by ucOC, and this effect was potentiated by an inhibitor of dipeptidyl peptidase IV and blocked by a GLP-1 receptor antagonist. Intravenous injection of ucOC in mice increased the serum GLP-1 concentration, and also increased the serum level of insulin. Our results suggest that ucOC acts via Gprc6a to induce GLP-1 release from the gut, and that the stimulatory effect of ucOC on insulin secretion is largely mediated by GLP-1.

  16. Osteocalcin Is Not Associated with the Risk of Type 2 Diabetes : Findings from the EPIC-NL Study

    NARCIS (Netherlands)

    Zwakenberg, Sabine R.; Gundberg, Caren M.; Spijkerman, Annemieke M. W.; van der A, Daphne L.; van der Schouw, Yvonne T.; Beulens, Joline W. J.

    2015-01-01

    Objective To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of type 2 diabetes. Methods This nested case control study included 1,635 participants, 833 incident diabetes cases and 802

  17. Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Sophie A. Millar

    2017-07-01

    Full Text Available BackgroundOsteocalcin (OC is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis.Methods and resultsDatabases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies. A higher percentage of Asian studies found a negative relationship (36% in contrast to European studies (6%. Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with “atherosclerosis” and control (p = 0.13, n = 1,197.ConclusionNo definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further

  18. Dimethyloxalylglycine Prevents Bone Loss in Ovariectomized C57BL/6J Mice through Enhanced Angiogenesis and Osteogenesis

    Science.gov (United States)

    Fang, Zhang Lian; Xing, Shen; Hui, Kang; Hao, Chen; Jin, Qi; Qi, Zhou; Shen, Wang Jin; Dong, Qian Nian; Bing, Zhou Han; Fu, Deng Lian

    2014-01-01

    Hypoxia-inducible factor 1-α (HIF-1α) plays a critical role in angiogenesis-osteogenesis coupling during bone development and bone regeneration. Previous studies have shown that 17β-estradiol activates the HIF-1α signaling pathway and that mice with conditional activation of the HIF-1α signaling pathway in osteoblasts are protected from ovariectomy (OVX)-induced bone loss. In addition, it has been shown that hypoxia facilitates the osteogenic differentiation of mesenchymal stem cells (MSCs) and modulates Wnt/β-catenin signaling. Therefore, we hypothesized that activation of the HIF-1α signaling pathway by hypoxia-mimicking agents would prevent bone loss due to estrogen deficiency. In this study, we confirmed the effect of dimethyloxalylglycine (DMOG), a hypoxia-mimicking agent, on the HIF-1α signaling pathway and investigated the effect of DMOG on MSC osteogenic differentiation and the Wnt/β-catenin signaling pathway. We then investigated the effect of DMOG treatment on OVX-induced bone loss. Female C57BL/6J mice were divided into sham, OVX, OVX+L-DMOG (5 mg/kg/day), and OVX+H-DMOG (20 mg/kg/day) groups. At sacrifice, static and dynamic bone histomorphometry were performed with micro computed tomography (micro-CT) and undecalcified sections, respectively. Bone strength was assessed with the three-point bending test, and femur vessels were reconstructed and analyzed by micro-CT. Serum vascular endothelial growth factor (VEGF), osteocalcin, and C-terminal telopeptides of collagen type(CTX) were measured by ELISA. Tartrate-resistant acid phosphatase staining was used to assess osteoclast formation. Alterations in the HIF-1α and Wnt/β-catenin signaling pathways in the bone were detected by western blot. Our results showed that DMOG activated the HIF-1α signaling pathway, which further activated the Wnt/β-catenin signaling pathway and enhanced MSC osteogenic differentiation. The micro-CT results showed that DMOG treatment improved trabecular bone density

  19. Effects of 12-week exercise training on osteocalcin, high-sensitivity C-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis.

    Science.gov (United States)

    Ahn, Nayoung; Kim, Kijin

    2016-08-01

    [Purpose] This study examined the effects of exercise training on bone metabolism markers, inflammatory markers, and physical fitness in patients with osteoporosis from an osteoporosis-related immunological perspective. [Subjects and Methods] Twenty-nine elderly female subjects (age, 74.2 ± 3.2 years) were classified into normal, osteopenia, and osteoporosis groups based on the T-score measured using dual-energy X-ray absorptiometry. The exercise was performed voluntarily by the patients for 1 hour per day, three times per week, for 12 weeks. [Results] The differences between bone mineral content, bone mineral density, and osteocalcin concentrations increased significantly in the osteoporosis group after 12 weeks of exercise and were significantly higher than those in the normal and osteopenia groups. However, the homeostatic model assessment of insulin resistance score decreased significantly in the osteoporosis group after 12 weeks of exercise. High-sensitivity C-reactive protein concentrations tended to decrease in all groups after 12 weeks of exercise and showed an inverse correlation with osteocalcin concentration; however, no statistical significance was observed. [Conclusion] Our findings suggest that an exercise program in patients with osteopenia and osteoporosis effectively reduces the risk of osteoporotic fracture and related diseases since it improves bone density and physical fitness and reduces inflammatory marker levels.

  20. Effects of 12-week exercise training on osteocalcin, high-sensitivity C-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis

    Science.gov (United States)

    Ahn, Nayoung; Kim, Kijin

    2016-01-01

    [Purpose] This study examined the effects of exercise training on bone metabolism markers, inflammatory markers, and physical fitness in patients with osteoporosis from an osteoporosis-related immunological perspective. [Subjects and Methods] Twenty-nine elderly female subjects (age, 74.2 ± 3.2 years) were classified into normal, osteopenia, and osteoporosis groups based on the T-score measured using dual-energy X-ray absorptiometry. The exercise was performed voluntarily by the patients for 1 hour per day, three times per week, for 12 weeks. [Results] The differences between bone mineral content, bone mineral density, and osteocalcin concentrations increased significantly in the osteoporosis group after 12 weeks of exercise and were significantly higher than those in the normal and osteopenia groups. However, the homeostatic model assessment of insulin resistance score decreased significantly in the osteoporosis group after 12 weeks of exercise. High-sensitivity C-reactive protein concentrations tended to decrease in all groups after 12 weeks of exercise and showed an inverse correlation with osteocalcin concentration; however, no statistical significance was observed. [Conclusion] Our findings suggest that an exercise program in patients with osteopenia and osteoporosis effectively reduces the risk of osteoporotic fracture and related diseases since it improves bone density and physical fitness and reduces inflammatory marker levels. PMID:27630402

  1. Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women.

    Science.gov (United States)

    Centi, Amanda J; Booth, Sarah L; Gundberg, Caren M; Saltzman, Edward; Nicklas, Barbara; Shea, M Kyla

    2015-12-01

    Osteocalcin (OC) is a vitamin K-dependent bone protein used as a marker of bone formation. Mouse models have demonstrated a role for the uncarboxylated form of OC (ucOC) in energy metabolism, including energy expenditure and adiposity, but human data are equivocal. The purpose of this study was to determine the associations between changes in measures of OC and changes in body weight and percent body fat in obese, but otherwise healthy post-menopausal women undergoing a 20-week weight loss program. All participants received supplemental vitamins K and D and calcium. Body weight and body fat percentage (%BF) were assessed before and after the intervention. Serum OC [(total (tOC), ucOC, percent uncarboxylated (%ucOC)], and procollagen type 1N-terminal propeptide (P1NP; a measure of bone formation) were measured. Women lost an average of 10.9 ± 3.9 kg and 4 %BF. Serum concentrations of tOC, ucOC, %ucOC, and P1NP did not significantly change over the twenty-week intervention, nor were these measures associated with changes in weight (all p > 0.27) or %BF (all p > 0.54). Our data do not support an association between any serum measure of OC and weight or %BF loss in post-menopausal women supplemented with nutrients implicated in bone health.

  2. Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

    Science.gov (United States)

    Nicolet-Barousse, Laurence; Blanchard, Anne; Roux, Christian; Pietri, Laurence; Bloch-Faure, May; Kolta, Sami; Chappard, Christine; Geoffroy, Valérie; Morieux, Caroline; Jeunemaitre, Xavier; Shull, Gary E; Meneton, Pierre; Paillard, Michel; Houillier, Pascal; De Vernejoul, Marie-Christine

    2005-05-01

    Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

  3. Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Lihui; Chen, Xi; Lv, Shuang; Dong, Miaomiao; Zhang, Li; Tu, Jiaheng; Yang, Jie; Zhang, Lingli; Song, Yinan; Xu, Leiting; Zou, Jun

    2014-01-01

    This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.

  4. Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and osteocalcin immunostaining of 22 cases.

    Science.gov (United States)

    Fanburg-Smith, Julie C; Auerbach, Aaron; Marwaha, Jayson S; Wang, Zengfeng; Rushing, Elisabeth J

    2010-05-01

    Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3 each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue; one each of femur, unspecified bone, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic

  5. Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls

    DEFF Research Database (Denmark)

    Cusack, S.; Mølgaard, C.; Michaelsen, K. F.

    2006-01-01

    (VDR) (FokI, TaqI) and estrogen receptor-alpha (ER alpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH...

  6. 骨钙素的研究进展及其与运动的联系%The Research Progress of Osteocalcin and the Contact with the Sports

    Institute of Scientific and Technical Information of China (English)

    徐勇; 王锋

    2011-01-01

    骨钙素(osteocalcin OC)也称为骨γ-梭基谷氨酸蛋白(bone γ-carboxyglutamicacid-con-tainingprotein,BGP)或骨Gla蛋白、骨依赖维生素K蛋白,主要是由非增殖期成骨细胞特异合成分泌的一种非胶质骨蛋白。本文仅对其最新研究进展及与运动的联系作一综述。%Osteocalcin, also known as bone γ-carboxyglutamicacid - containingprotein, BGP Gla and so on, is a structure protein synthesized by osteoblasts,Mainly by the non proliferation stage osteoblast specific synthesis secretion of a non gelatinous bone protein.This article discusses its latest research progress and takes a review of the contact with the sports.

  7. Invasive versus non-invasive diagnosis of renal bone disease.

    Science.gov (United States)

    Fournier, A; Oprisiu, R; Said, S; Sechet, A; Ghazali, A; Marié, A; el Esper, I; Brazier, M; Achard, J M; Morinière, P

    1997-07-01

    At present, bone histomorphometry remains the gold standard for the diagnosis of the various types of renal bone disease. In the search for a non-invasive method of diagnosis, biochemical serum markers of bone remodelling, in addition to serum intact parathyroid hormone and aluminium determinations, have been proposed as the most reliable tools and are at present widely used in clinical practice. Their respective diagnostic values, as separate items and in combined analysis, are thoroughly discussed in the present review.

  8. Vitamin K nutritional status and undercarboxylated osteocalcin in postmenopausal osteoporotic women treated with bisphosphonates.

    Science.gov (United States)

    Iwamoto, Jun; Takada, Tetsuya; Sato, Yoshihiro

    2014-01-01

    Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional status in treatment-naive postmenopausal osteoporotic women. The purpose of the present study was to reveal the association between vitamin K nutritional status and serum ucOC concentrations in postmenopausal osteoporotic women taking bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47-90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was evaluated using a simple vitamin K-intake questionnaire and serum ucOC concentrations were measured after 6 months of treatment. The patients were divided into two groups according to the simple vitamin K-intake questionnaire score: a low vitamin K-intake (score =40) group (n=19). There were no significant differences between the groups in baseline parameters including age, height, body weight, body mass index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX concentrations during the 6-month treatment period. However, the mean serum ucOC concentration after 6 months of treatment was significantly higher in the low vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women treated with bisphosphonates may have vitamin K deficiency as indicated by low vitamin K-intake and high serum ucOC concentrations, despite having a similar reduction in bone turnover to women who have normal vitamin K-intake.

  9. Cartilage histomorphometry.

    Science.gov (United States)

    Hunziker, Ernst B

    2007-01-01

    In rheumatology and joint research, as in other fields, a purely descriptional appqoach to morphology cannot satisfy the exactions of modern clinical medicine. Investigators now appreciate the need to gauge pathological changes and their response to treatment by quantifying susceptible structural parameters. But the desired information respecting three-dimensional structures must be gleaned from either actual or virtual two-dimensional sections through the tissue. This information can be obtained only if the laws governing stereology are respected. In this chapter, the stereological principles that must be applied, and the practical methods that have been devised, to yield unbiased estimates of the most commonly determined structural parameters, namely, volume, surface area and number, are summarized.

  10. The effects of dietary supplementation during pregnancy on placental morphology, pathology, and histomorphometry.

    Science.gov (United States)

    Rush, D; Kristal, A; Navarro, C; Chauhan, P; Blanc, W; Naeye, R; Susser, M W

    1984-06-01

    We related the macroscopic and microscopic morphology and the histomorphometry of the placenta to prenatal nutritional supplementation. In the Prenatal Project, a controlled clinical trial, three dietary treatments (supplement, a high-protein beverage; complement, a balanced protein-calorie beverage, or routine vitamin and mineral tablets) were randomly allocated to poor Black pregnant women, and the outcome was assessed. Herein we report the effects on placental morphology and histomorphometry. There were significantly fewer preterm deliveries in the complement group, and this was reflected by an increase in the size of decidual cells, an index associated with placental aging. Several other characteristics of the placentas of the complement group may have been more directly associated with improved perinatal outcome: decreased intervillous fibrin, lower incidence of gross surface infarct, and smaller (and presumably less edematous) cells of the villous stroma, may have mediated increased placental perfusion. There was no evidence of any placental change associated with the increase in very preterm delivery and the highly significant depressed birth weight among preterm deliveries in the supplement group. The significantly lower incidence of meconium staining of Wharton's jelly among controls seems likely to have been a chance finding. While there were several other indices that reflected placental aging, the significantly increased chorioamnionitis, acute funisitis , and acute decidual inflammation among placentas of those who delivered prematurely [the former two associated with very early delivery (less than 35 wk gestation)] were likely to have been involved as causes of premature delivery.

  11. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

    Science.gov (United States)

    Guo, Qinyue; Fan, Ping; Luo, Jing; Wu, Shufang; Sun, Hongzhi; He, Lan; Zhou, Bo

    2017-03-01

    Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

  12. Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

    Directory of Open Access Journals (Sweden)

    J O Eniwumide

    2007-08-01

    Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

  13. Correlation between serum osteocalcin and type 2 diabetes mellitus in elderly patients

    Institute of Scientific and Technical Information of China (English)

    邓捷

    2013-01-01

    Objective To investigate the correlation between serum osteocalcin and type 2 diabetes mellitus (T2DM) in elderly patients.Methods A total of 55 T2DM patients (diabetic group) and 50 non-diabetic subjects (control group) aged≥60 years were enrolled in this study.The

  14. GPRC6A Mediates Responses to Osteocalcin in β-Cells In Vitro and Pancreas In Vivo

    Science.gov (United States)

    Pi, Min; Wu, Yunpeng; Quarles, L Darryl

    2016-01-01

    A bone-pancreas endocrine loop has been identified recently that involves insulin secreted from β-cells in the pancreas stimulating insulin receptors in osteoblasts, leading to osteoblastic differentiation and increased secretion of osteocalcin (Ocn), a bone-derived hormone that regulates insulin secretion in β-cells. The identity of the Ocn-sensing receptor in β-cells is a missing component of this endocrine loop. The abnormalities in glucose homeostasis in Gprc6a null mice suggests that this pertussis toxin–sensitive G protein– coupled receptor is a candidate for mediating the effects of Ocn on insulin secretion in the pancreas. In support of this possibility, we found that transfection of non-Gprc6a-expressing HEK-293 cells with a full-length Gprc6a cDNA imparted a dose-dependent response to Ocn (5 to 60 ng/mL), as measured by PKD1 and ERK phosphorylation. In addition, Gprc6a is highly expressed in mouse pancreatic tissue and in the mouse TC-6 pancreatic β-cell line. Ocn also stimulated ERK activity in TC-6 pancreatic β-cells. Finally, intraperitoneal injection of Ocn stimulated ERK activity in the pancreas and increased serum insulin levels in wild-type mice, but these responses were markedly attenuated in Gprc6a−/− mice. These findings suggest that GPRC6A is a candidate for mediating the response to Ocn in the bone-pancreas endocrine loop regulating insulin signaling. PMID:21425331

  15. Thiazide diuretics affect osteocalcin production in human osteoblasts at the transcription level without affecting vitamin D3 receptors.

    Science.gov (United States)

    Lajeunesse, D; Delalandre, A; Guggino, S E

    2000-05-01

    Besides their natriuretic and calciuretic effect, thiazide diuretics have been shown to decrease bone loss rate and improve bone mineral density. Clinical evidence suggests a specific role of thiazides on osteoblasts, because it reduces serum osteocalcin (OC), an osteoblast-specific protein, yet the mechanisms implicated are unknown. We therefore investigated the role of hydrochlorothiazide (HCTZ) on OC production by the human osteoblast-like cell line MG-63. HCTZ dose-dependently (1-100 microM) inhibited 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced OC release by these cells (maximal effect, -40-50% and p ethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) only partly prevented the inhibitory effect of the diuretic on OC secretion (maximal effect, -22.5+/-6.9%), suggesting that thiazide-dependent Ca2+ influx is not sufficient to elicit the inhibition of OC secretion. Because OC production is strictly dependent on the presence of 1,25(OH)2D3 in human osteoblasts, we next evaluated the possible role of HCTZ on vitamin D3 receptors (VDR) at the mRNA and protein levels. Both Northern and Western blot analyses showed no effect of HCTZ (1-100 microM) on VDR levels. The presence of EGTA in the culture media reduced slightly the VDR mRNA levels under basal condition but this was not modified in the presence of increasing levels of HCTZ. The OC gene promoter also is under the control of transcription factors such as Yin Yang 1 (YY1) and cFOS. Western blot analysis revealed no changes in YY1 levels in response to HCTZ either in the presence or in the absence of 0.5 mM EGTA in the culture media. In contrast, HCTZ induced a dose-dependent increase in cFOS levels (p production by HCTZ could explain its preventive role in bone loss rate.

  16. Disassociation of bone resorption and formation by GLP-2

    DEFF Research Database (Denmark)

    Henriksen, Dennis B; Alexandersen, Peter; Hartmann, Bolette

    2007-01-01

    of collagen type I (s-CTX and u-CTX) and u-DPD, markers of bone resorption. In contrast, bone formation, as assessed by serum osteocalcin and procollagen type I N-terminal propeptide (PINP), appeared to be unaffected by treatment with exogenous GLP-2. These effects were further investigated in a 14-day study...

  17. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    Science.gov (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  18. The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China.

    Science.gov (United States)

    Ba, Yue; Huang, Hui; Yang, Yuejin; Cui, Liuxin; Zhu, Jingyuan; Zhu, Cairong; Liu, Jie; Zhang, Yawei

    2009-11-01

    Excessive fluoride intake has been shown to affect dentin and cementum mineralization throughout life. Some studies indicated that a HindIII polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism-related diseases. Therefore, it is possible that the variation in OC genotypes will be associated with dental fluorosis (DF) status and/or serum caciotropic hormone level. A case-control study was conducted among children aged 8-12 years in Henan Province, PR China to investigate the association between dental fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene. HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC and calcitonin (CT) level in serum was detected using radioimmunoassay. No significant difference was observed for OC HindIII genotypes among the cases with dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls from non-endemic fluorosis area (NEFA). A significant negative correlation was observed between serum calcium and OC level. No significant relationship was found between OC HindIII polymorphisms and the level of OC and CT. In conclusion, OC HindIII polymorphisms may not be a useful genetic marker for differential risk of dental fluorosis among children in PR China.

  19. Use of carboxymethyl cellulose and collagen carrier with equine bone lyophilisate suggests late onset bone regenerative effect in a humerus drill defect - a pilot study in six sheep

    DEFF Research Database (Denmark)

    Jensen, Jonas; Foldager, Casper Bindzus; Jakobsen, Thomas Vestergaard;

    2010-01-01

    in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (microCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site...

  20. Histomorphometry of hepatic portal fibrosis in patients with surgical schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Brandt Carlos Teixeira

    2002-01-01

    Full Text Available The usual histology report of hepatic fibrosis in patients with hepatosplenic schistosomiasis mansoni presents no association with hemodynamic and clinical liver parameters. Histomorphometry is adding a new tool of investigation for measuring density of portal fibrosis in these patients. This investigation was set up for assessing a possible agreement between the well-accepted international classification and the fibrosis density grades measured by histomorphometry. Thirty-five children and equal number of adults were included in this study. All patients underwent splenectomy and ligature of the left gastric vein. Histology findings were assessed in surgical liver biopsy stained with Masson trichrome. The official histology report was used as reference. The histomorphometric studies were done by semi-automatic morphometry. The mean percentage (X of portal fibrosis plus or minus one standard deviation (SD was classified as grade II (7.06% up to 34.72%; grade I was up to 7.06%; and grade III above 34.72%. Although, not reaching statistical significance, there is a tendency of the fibrosis to be more intense in children than adults (X±SD - 22.02±13.46% versus 20.63%±15.33% "t" = 0.379 p>0.05. Seven out of nine (77.8% patients classified as grade I, by morphometry, had the same result on the official report, however, two (22.2% were described as grade III. Sixteen out of forty-four (36.4% classified as grade II on morphometry had the same classification as the histology grade, but, twenty seven (61.4% were classified as grade III and one (2.3% as grade I. Fifteen (21.4% out of 70 patients had grade III on both classifications, but, two (11.8% out of seventeen G III on morphometry were grade II. The kappa (k measurement of agreement between both classification was k = 0.319, showing a fair strength of association. The histomorphometric measurements of Symmers fibrosis in surgical patients with mansonic schistosomiasis partially support the report

  1. 颞下颌关节紊乱病关节液雌二醇及骨钙素的检测及其临床意义%Osteocalcin and estradiol in synovial fluid of the patients with temporomandibular disorders

    Institute of Scientific and Technical Information of China (English)

    程鹏; 马绪臣; 李盛琳; 薛延

    2001-01-01

    control and ID (P<0.05).Synovial fluid E2 was found in all patients and controls.The concentration of synovial E2 was significant higher in ID and OA than that of normal control,but there was no significant difference in synovial E2 level between ID and OA.Synovial E2 level was much higher in TMJs with osteosclerotic change and no difference between male and female patients with TMD.Conclusion These results suggest that estrogen could be involved in the pathogenesis and development of TMD.High level of synovial estradiol may contribute to osteoselerotic change of TMJs.Meanwhile,TMJOA may relate to local increase of bone turnover and abnormalities of bone metabolism.Quantification of osteocalcin in synovial fluid holds promise as a useful means of assesing the alteration of bone at the molecular level in the patients with TMD.

  2. Osteocalcin induces growth hormone/insulin-like growth factor-1 system by promoting testosterone synthesis in male mice.

    Science.gov (United States)

    Li, Y; Li, K

    2014-10-01

    Osteocalcin has been shown to enhance testosterone production in men. In the present study, we investigated the effects of osteocalcin on testosterone and on induction of the growth hormone/insulin-like growth factor-1 axis. Osteocalcin injection stimulated growth, which could be inhibited by castration. In addition, osteocalcin induced testosterone secretion in testes both in vivo and in vitro. Using real-time polymerase chain reaction and Western blotting, we showed that growth hormone expression was significantly increased in the pituitary after osteocalcin injection (pGrowth hormone expression in CLU401 mouse pituitary cells was also significantly stimulated (pgrowth hormone receptor and insulin-like growth factor-1 (pgrowth hormone receptor and insulin-like growth factor-1 expression in NCTC1469 cells. These results suggest that the growth-stimulating activities of osteocalcin are mediated by testicular testosterone secretion, and thus provide valuable information regarding the regulatory effects of osteocalcin expression on the growth hormone/insulin-like growth factor-1 axis via reproductive activities.

  3. 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.J.; Verdonschot, N.J.; 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 bon

  4. 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.J.; Verdonschot, N.J.; 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

  5. Osteocalcin, but not deoxypyridinoline, increases in response to isoflurane-induced anaesthesia in young female guinea pigs.

    Science.gov (United States)

    Tabatabaei, Negar; Rodd, Celia J; Kremer, Richard; Weiler, Hope A

    2015-05-01

    The effect of the inhaled anaesthetic isoflurane was investigated on bone biomarkers, both during maturation and on minerals and glucose postpartum. Female guinea pigs (n = 10) were anaesthetized during maturation (5 and 9 weeks) and postpartum (26 weeks of age) with isoflurane during dual-energy X-ray absorptiometry scanning. Blood collection was performed at all ages before and after anaesthesia for measurement of plasma osteocalcin (OC), total deoxypyridinoline (tDPD), and cortisol. Postpartum measurements also included: blood ions, acid-base parameters and glucose, plasma minerals, total alkaline phosphatase (tALP), and albumin. Plasma OC concentration almost doubled after exposure to isoflurane at 5 weeks (30.1 ± 5.0-57.9 ± 11.2 nmol/L, p  0.05). Blood ionized Ca(2+), Na(+) and plasma total Ca did not change, whereas plasma albumin decreased, and inorganic phosphate (PO4) and Cl(-) increased upon exposure to isoflurane. Isoflurane decreased tALP (43.2 ± 6.6-40.2 ± 5.9 IU/L, p = 0.01) and increased glucose (7.5 ± 0.6-10.9 ± 1.7 mmol/L, p < 0.0001) postpartum. Isoflurane inflates the assessment of a bone-derived biomarker, OC, during rapid growth, but not following pregnancy when formation is very low. Measurements prior to anaesthesia are recommended to reflect normal metabolism.

  6. Effects of Tai Ji Exercise on Bone Structure and Function

    Institute of Scientific and Technical Information of China (English)

    Xu Hong; David Lawson

    2005-01-01

    To evaluated the effects of the 24 movements Tai Ji exercise on bone structure and function. Broadband Ultrsonic Attenuation (BUA) and velocity of sound (VOS), bone formation marker Osteocalcin (OSTN) and bone resorption markers urinary Pyridum crosslinks (PYR and D-PYR) were studied before and after four months of Tai Ji exercise. Improved bone structure and increased bone density in menopausal women were reflected by BUA results. The increased BUA appears to be associated with increased bone formation rather than decreased bone resorption.

  7. Histomorphometry of the tibia and mandible of healthy female Wistar rats at different stages of growth.

    Science.gov (United States)

    Nenda, María M; Lewicki, Marianela; Mandalunis, Patricia M

    2016-05-20

    Female Wistar rats are frequently used in experimental models to study hormone and bone pathologies and treatments. Most experimental studies involving histomorphometric evaluation assessed long bones, and few reports also studied mandibular bone. The aim of this work was to clarify and distinguish the age-related histomorphometric changes that occur in the tibia (subchondral bone) and in the mandible (interradicular bone), and thus obtain reference histomorphometric data of healthy female Wistar rats at different growth stages. Three groups of 8 healthy female Wistar rats were euthanized at 6 (GI), 10 (GII), and 14 (GIII) weeks. The tibiae and mandible were resected and histologically processed to obtain H&E stained sections of the tibia and the lower first molar to analyze the following histomorphometric parameters: Bone volume, trabecular width, trabecular number (Th.N)(1/mm), growth cartilage width, hypertrophic cartilage width and number of osteoclasts per area in the tibiae, and bone volume and number of osteoclasts per area N.Oc/mm(2) in the interradicular bone of the first lower molar. A significant decrease in subchondral bone volume as a result of a decrease in trabecular number and growth cartilage width was observed in 14-week-old rats. Conversely, interradicular bone volume was found to increase with age. The results highlight the importance of analyzing both types of bone to better understand the response of two different trabecular bones, contributing in turn to decision making regarding treatment strategies and disease management.

  8. Decellularized bone matrix grafts for calvaria regeneration

    Science.gov (United States)

    Lee, Dong Joon; Diachina, Shannon; Lee, Yan Ting; Zhao, Lixing; Zou, Rui; Tang, Na; Han, Han; Chen, Xin; Ko, Ching-Chang

    2016-01-01

    Decellularization is a promising new method to prepare natural matrices for tissue regeneration. Successful decellularization has been reported using various tissues including skin, tendon, and cartilage, though studies using hard tissue such as bone are lacking. In this study, we aimed to define the optimal experimental parameters to decellularize natural bone matrix using 0.5% sodium dodecyl sulfate and 0.1% NH4OH. Then, the effects of decellularized bone matrix on rat mesenchymal stem cell proliferation, osteogenic gene expression, and osteogenic differentiations in a two-dimensional culture system were investigated. Decellularized bone was also evaluated with regard to cytotoxicity, biochemical, and mechanical characteristics in vitro. Evidence of complete decellularization was shown through hematoxylin and eosin staining and DNA measurements. Decellularized bone matrix displayed a cytocompatible property, conserved structure, mechanical strength, and mineral content comparable to natural bone. To study new bone formation, implantation of decellularized bone matrix particles seeded with rat mesenchymal stem cells was conducted using an orthotopic in vivo model. After 3 months post-implantation into a critical-sized defect in rat calvaria, new bone was formed around decellularized bone matrix particles and also merged with new bone between decellularized bone matrix particles. New bone formation was analyzed with micro computed tomography, mineral apposition rate, and histomorphometry. Decellularized bone matrix stimulated mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo, achieving effective bone regeneration and thereby serving as a promising biological bone graft. PMID:28228929

  9. Decellularized bone matrix grafts for calvaria regeneration

    Directory of Open Access Journals (Sweden)

    Dong Joon Lee

    2016-12-01

    Full Text Available Decellularization is a promising new method to prepare natural matrices for tissue regeneration. Successful decellularization has been reported using various tissues including skin, tendon, and cartilage, though studies using hard tissue such as bone are lacking. In this study, we aimed to define the optimal experimental parameters to decellularize natural bone matrix using 0.5% sodium dodecyl sulfate and 0.1% NH4OH. Then, the effects of decellularized bone matrix on rat mesenchymal stem cell proliferation, osteogenic gene expression, and osteogenic differentiations in a two-dimensional culture system were investigated. Decellularized bone was also evaluated with regard to cytotoxicity, biochemical, and mechanical characteristics in vitro. Evidence of complete decellularization was shown through hematoxylin and eosin staining and DNA measurements. Decellularized bone matrix displayed a cytocompatible property, conserved structure, mechanical strength, and mineral content comparable to natural bone. To study new bone formation, implantation of decellularized bone matrix particles seeded with rat mesenchymal stem cells was conducted using an orthotopic in vivo model. After 3 months post-implantation into a critical-sized defect in rat calvaria, new bone was formed around decellularized bone matrix particles and also merged with new bone between decellularized bone matrix particles. New bone formation was analyzed with micro computed tomography, mineral apposition rate, and histomorphometry. Decellularized bone matrix stimulated mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo, achieving effective bone regeneration and thereby serving as a promising biological bone graft.

  10. Type 2 diabetes mellitus impairs bone healing of dental implants in GK rats.

    Science.gov (United States)

    Wang, Feng; Song, Ying-liang; Li, De-hua; Li, Cui-xia; Wang, Yao; Zhang, Ning; Wang, Bao-gang

    2010-04-01

    Type 2 diabetes is an increasingly prevalent disease with oral health manifestations. In this study, titanium implants were placed in the femora of 10 type 2 diabetic and 10 age-matched normal rats. We compared the results of bone histomorphometry around the dental implants at 4 and 8 weeks postsurgery.

  11. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone...... within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...... that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site...

  12. Gingival Crevicular Fluid Calprotectin, Osteocalcin and Cross-Linked N-Terminal Telopeptid Levels in Health and Different Periodontal Diseases

    Directory of Open Access Journals (Sweden)

    Sema Becerik

    2011-01-01

    Full Text Available Aim: The aim of the present study was to investigate gingival crevicular fluid (GCF calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx levels in health along with different periodontal diseases.

  13. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  14. Accuracy and sampling error of two age estimation techniques using rib histomorphometry on a modern sample.

    Science.gov (United States)

    García-Donas, Julieta G; Dyke, Jeffrey; Paine, Robert R; Nathena, Despoina; Kranioti, Elena F

    2016-02-01

    Most age estimation methods are proven problematic when applied in highly fragmented skeletal remains. Rib histomorphometry is advantageous in such cases; yet it is vital to test and revise existing techniques particularly when used in legal settings (Crowder and Rosella, 2007). This study tested Stout & Paine (1992) and Stout et al. (1994) histological age estimation methods on a Modern Greek sample using different sampling sites. Six left 4th ribs of known age and sex were selected from a modern skeletal collection. Each rib was cut into three equal segments. Two thin sections were acquired from each segment. A total of 36 thin sections were prepared and analysed. Four variables (cortical area, intact and fragmented osteon density and osteon population density) were calculated for each section and age was estimated according to Stout & Paine (1992) and Stout et al. (1994). The results showed that both methods produced a systemic underestimation of the individuals (to a maximum of 43 years) although a general improvement in accuracy levels was observed when applying the Stout et al. (1994) formula. There is an increase of error rates with increasing age with the oldest individual showing extreme differences between real age and estimated age. Comparison of the different sampling sites showed small differences between the estimated ages suggesting that any fragment of the rib could be used without introducing significant error. Yet, a larger sample should be used to confirm these results. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation

    Directory of Open Access Journals (Sweden)

    Bensimon-Brito Anabela

    2012-10-01

    Full Text Available Abstract Background In chondrichthyans, basal osteichthyans and tetrapods, vertebral bodies have cartilaginous anlagen that subsequently mineralize (chondrichthyans or ossify (osteichthyans. Chondrocytes that form the vertebral centra derive from somites. In teleost fish, vertebral centrum formation starts in the absence of cartilage, through direct mineralization of the notochord sheath. In a second step, the notochord is surrounded by somite-derived intramembranous bone. In several small teleost species, including zebrafish (Danio rerio, even haemal and neural arches form directly as intramembranous bone and only modified caudalmost arches remain cartilaginous. This study compares initial patterns of mineralization in different regions of the vertebral column in zebrafish. We ask if the absence or presence of cartilaginous arches influences the pattern of notochord sheath mineralization. Results To reveal which cells are involved in mineralization of the notochord sheath we identify proliferating cells, we trace mineralization on the histological level and we analyze cell ultrastructure by TEM. Moreover, we localize proteins and genes that are typically expressed by skeletogenic cells such as Collagen type II, Alkaline phosphatase (ALP and Osteocalcin (Oc. Mineralization of abdominal and caudal vertebrae starts with a complete ring within the notochord sheath and prior to the formation of the bony arches. In contrast, notochord mineralization of caudal fin centra starts with a broad ventral mineral deposition, associated with the bases of the modified cartilaginous arches. Similar, arch-related, patterns of mineralization occur in teleosts that maintain cartilaginous arches throughout the spine. Throughout the entire vertebral column, we were able to co-localize ALP-positive signal with chordacentrum mineralization sites, as well as Collagen II and Oc protein accumulation in the mineralizing notochord sheath. In the caudal fin region, ALP and

  16. Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation

    Science.gov (United States)

    2012-01-01

    Background In chondrichthyans, basal osteichthyans and tetrapods, vertebral bodies have cartilaginous anlagen that subsequently mineralize (chondrichthyans) or ossify (osteichthyans). Chondrocytes that form the vertebral centra derive from somites. In teleost fish, vertebral centrum formation starts in the absence of cartilage, through direct mineralization of the notochord sheath. In a second step, the notochord is surrounded by somite-derived intramembranous bone. In several small teleost species, including zebrafish (Danio rerio), even haemal and neural arches form directly as intramembranous bone and only modified caudalmost arches remain cartilaginous. This study compares initial patterns of mineralization in different regions of the vertebral column in zebrafish. We ask if the absence or presence of cartilaginous arches influences the pattern of notochord sheath mineralization. Results To reveal which cells are involved in mineralization of the notochord sheath we identify proliferating cells, we trace mineralization on the histological level and we analyze cell ultrastructure by TEM. Moreover, we localize proteins and genes that are typically expressed by skeletogenic cells such as Collagen type II, Alkaline phosphatase (ALP) and Osteocalcin (Oc). Mineralization of abdominal and caudal vertebrae starts with a complete ring within the notochord sheath and prior to the formation of the bony arches. In contrast, notochord mineralization of caudal fin centra starts with a broad ventral mineral deposition, associated with the bases of the modified cartilaginous arches. Similar, arch-related, patterns of mineralization occur in teleosts that maintain cartilaginous arches throughout the spine. Throughout the entire vertebral column, we were able to co-localize ALP-positive signal with chordacentrum mineralization sites, as well as Collagen II and Oc protein accumulation in the mineralizing notochord sheath. In the caudal fin region, ALP and Oc signals were clearly

  17. One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption.

    Science.gov (United States)

    Varela, Aurore; Chouinard, Luc; Lesage, Elisabeth; Smith, Susan Y; Hattersley, Gary

    2017-01-01

    Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss. Ten OVX rats were euthanized after this bone depletion period, and the remaining OVX rats received daily subcutaneous injections of vehicle (n = 18) or abaloparatide at 1, 5, or 25 μg/kg/d (n = 18/dose level) for 12 months. Sham controls (n = 18) received vehicle daily. Bone densitometry and biochemical markers of bone formation and resorption were assessed longitudinally, and L3 vertebra and tibia were collected at necropsy for histomorphometry. Abaloparatide increased biochemical bone formation markers without increasing bone resorption markers or causing hypercalcemia. Abaloparatide increased histomorphometric indices of bone formation on trabecular, endocortical, and periosteal surfaces without increasing osteoclasts or eroded surfaces. Abaloparatide induced substantial increases in trabecular bone volume and density and improvements in trabecular microarchitecture. Abaloparatide stimulated periosteal expansion and endocortical bone apposition at the tibial diaphysis, leading to marked increases in cortical bone volume and density. Whole-body bone mineral density (BMD) remained stable in OVX-Vehicle controls while increasing 25% after 12 months of abaloparatide (25 μg/kg). Histomorphometry and biomarker data suggest that gains in cortical and trabecular bone mass were attributable to selective anabolic effects of abaloparatide, without evidence for stimulated bone resorption. © 2016 American Society for Bone and Mineral Research.

  18. The Effect of Conditional Inactivation of Beta 1 Integrins using Twist 2 Cre, Osterix Cre and Osteocalcin Cre Lines on Skeletal Phenotype

    Science.gov (United States)

    Shekaran, Asha; Shoemaker, James T.; Kavanaugh, Taylor E.; Lin, Angela S.; LaPlaca, Michelle C.; Fan, Yuhong; Guldberg, Robert E.; García, Andrés J.

    2014-01-01

    Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and Osteocalcin-Cre lines to generate conditional β1 integrin deletions, where cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic

  19. The increasing of fibroblast growth factor 2, osteocalcin, and osteoblast due to the induction of the combination of Aloe vera and 2% xenograft concelous bovine

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2012-12-01

    Full Text Available Background: To make a successfull denture prominent ridge is needed, preservation on tooth extraction socket is needed in order to prevent alveol bone resorption caused by revocation trauma. An innovative modification of the material empirically suspected to be able reduce inflammation caused by the revocation trauma is a combination of Aloe vera and xenograft concelous bovine (XCB and Aloe vera is a biogenic stimulator and accelerating the growth of alveolar ridge bone after tooth extraction. Purpose: The research was aimed to determine of the increasing alveol bone formation by inducing the combination of Aloe vera and 2% xenograft concelous bovine. Methods: To address the problems, the combination of Aloe vera and xenograft concelous bovine was induced into the tooth extraction sockets of Cavia cabayas which devided on 8 groups. Groups control, filled with XCB, Aloe vera and Aloe vera and XCB combination, at 7 days and 30 days after extraction. Afterwards, immunohistochemical examination was conducted to examine the expressions of FGF-2 and osteocalcin, as the product of the growth of osteoblasts. Results: There were significantly increases expression of FGF-2 and osteocalcyn on group which filled with XCB, Aloe vera and combined Aloe vera and XCB. Conclusion: It may be concluded that the induction of the combination of Aloe vera and xenograft concelous bovine into the tooth sockets can enhance the growth expressions of FGF-2 and osteocalcin as the product of osteoblasts, thus, the growth of alveolar bone was increased.Latar belakang: Untuk keberhasilan pembuatan gigitiruan diperlukan ridge yang prominent, maka diperlukan suatu preservasi soket pencabutan gigi untuk mencegah terjadinya resopsi tulang alveolar akibat trauma pencabutan. Suatu inovasi modifikasi bahan yang diduga secara empiris dapat mengurangi keradangan karena trauma pencabutan adalah berupa kombinasi Aloe vera dan xenograft concelous bovine (XCB. Aloe vera yang merupakan

  20. Osteoarthritis and bone: Osteologic types of osteoarthritis of the hip

    Energy Technology Data Exchange (ETDEWEB)

    Oettmeier, R.; Abendroth, K.

    1989-05-01

    To assess prognosis and indications for allografting articular surfaces, osteological examination is of increasing importance. In this study 93 femoral heads of patients with primary osteoarthritis could be differentiated into three osteologic types using histomorphometry: (1) the osteosclerotic type (77% of cases), (2) the hyperostotic type, with excessive neogenesis of bone all over the femoral head and increased formation of osteophytes (10% of cases), and (3) the osteopenic type, with decreased bone mass and features of bone remodelling, a greater occurrence of subchondral cysts, and small osteophytes (8% of cases). Radiological and clinical features to distinguish these groups are given. The consequences for pathogenesis and clinical practice are discussed. (orig.).

  1. 1,25(OH)2D3 inhibits the deleterious effects induced by high glucose on osteoblasts through undercarboxylated osteocalcin and insulin signaling.

    Science.gov (United States)

    Wu, Ying-ying; Yu, Tao; Zhang, Xiao-hui; Liu, Yan-shan; Li, Feng; Wang, Yan-ying; Wang, Yong-yue; Gong, Ping

    2012-10-01

    Diabetes mellitus (DM) is associated with multiple skeletal disorders, and vitamin D may play a functional role in the preservation of glucose tolerance. However, the relationship between vitamin D deficiency and DM is not well known. The aim of this study was to investigate the potential molecular link between 1,25(OH)(2)D(3) regulation and glucose homeostasis. Rat primary osteoblasts were cultured in different conditioned medium: normal glucose, high glucose, high glucose and insulin, high glucose and 1,25(OH)(2)D(3), high glucose and insulin and 1,25(OH)(2)D(3). The activity of osteoblasts was measured by cell viability, alkaline phosphatase and osteocalcin assay. The potential mechanism of how 1,25(OH)(2)D(3) affect insulin sensitivity was investigated by the assay of insulin receptor (IR) and vitamin D receptor (VDR) expression, and undercarboxylated osteocalcin (ucOC) level. The combined treatment has the strongest effect of inhibiting the deleterious effects induced by high glucose on osteoblasts, and it promoted the %ucOC value to approximately 40%, which is much higher than that in high glucose without treatment. Levels of IR and VDR of osteoblasts in combined treatment culture increased significantly compared with that in high glucose without treatment. So maybe 1,25(OH)(2)D(3) promotes insulin sensitivity of osteoblasts by activating insulin signaling and simultaneously stimulating ucOC secretion, which in turn regulate insulin production and sensitivity. 1,25(OH)(2)D(3) might be beneficial not only for diabetes, but also, for osteoporosis by promoting bone formation.

  2. Bone markers after total body irradiation in childhood.

    Science.gov (United States)

    Couto-Silva, A-C; Trivin, C; Espérou, H; Michon, J; Baruchel, A; Souberbielle, J-C; Brauner, R

    2010-03-01

    Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6+/-0.4 years were evaluated at 9.8+/-0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, rho=0.42, P=0.0007; osteocalcin with CTX, rho=0.3, Pirradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.

  3. Efficacy of early chick nutrition with Aloe vera and Azadirachta indica on gut health and histomorphometry in chicks

    Science.gov (United States)

    Sujatha, Tamilvanan; Abhinaya, Sivasankar; Sunder, Jai; Thangapandian, Marudhai; Kundu, Anandamoy

    2017-01-01

    Aim: This study was conducted with an aim of studying the efficacy of water supplements of Aloe vera and Azadirachta indica (neem) during pre-starter age (0-2 weeks) on gut health and histomorphometry in Vanaraja chicks. Materials and Methods: A total of 192 day old Vanaraja chicks were randomly assigned to one of four herbal water treatments throughout the experimental pre-starter stage (0-2 weeks) in a completely randomized design. Each treatment was given four replicates consisting of 12 chicks per replicate. Water treatments comprised T1: Control with regular antibiotic supplement, T2: 3 ml Aloe juice per chick per day, T3: 3 ml neem extract per chick per day, T4: 1.5 ml Aloe and 1.5 ml neem per chick per day. Gut culture was done for Escherichia coli and Lactobacillus sps. and gut histomorphometry in 24 gut samples at 14 days of age. Results: This study revealed that supplementation of A. vera and neem in water significantly (pneem supplementation as compared to that of control chicks. Significantly lower crypt depth (pneem and Aloe supplementation in chicks as compared to their combination and control. Conclusion: Immediate post hatch supplementation of Aloe juice and neem extract in chicks improved the development and health of their gut. PMID:28717305

  4. Studi Histologi dan Histomorfometri Daging Sapi Bali dan Wagyu (HISTOLOGYCAL AND HISTOMORPHOMETRY STUDY OF BALI CATTLE AND WAGYU BEEF

    Directory of Open Access Journals (Sweden)

    Ni Ketut Suwiti

    2015-10-01

    Full Text Available The objective of this study was to detect histological structure and histomorphometry of bali cattleand wagyu beef. The samples were collected from rib eye muscle of wagyu and bali cattle. The tissuesamples were fixed, dehydrated and embedded in paraffin and 4-5 mm sections, for histological examinationand stained with Haematoxilin-Eosin (HE. The light binocular microscope was used to identify the samples.The study showed that the beef histological structure consisted of: cells / muscle fibers, fatty and connectivetissues. The muscle fibers of wagyu were observed larger, regular, and longer compared to the Bali cattle.Additionally, intramuscular fat cells and connective tissue interlobulus were found less and thinner thanthe Bali cattle. In the area of muscle where the longitudinal cut was done, its observed that the presence ofI and A bands in Bali cattle beef were clearer compared to the wagyu. The diameter muscle fibers of balicattle beef (45.00 ±1.94 ?m, was smaller (P < 0.01 compared to the wagyu (75.00±1.82 ?m, as well as fatcell size of bali cattle beef (90.10 ±2.13 ?m and wagyu beef (195.00±2.57?m. In conclusion, the structureof histology and histomorphometry of rib eye muscle in Bali cattle were different to the wagyu.

  5. Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

    Science.gov (United States)

    Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2006-02-01

    Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)

  6. Nanoscale characterization of bone-implant interface and biomechanical modulation of bone ingrowth

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Paul A. [Tissue Engineering Laboratory MC 841, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, 801 South Paulina Street, Illinois 60612 (United States)]. E-mail: pclark4@gmail.com; Clark, Andrew M. [Tissue Engineering Laboratory MC 841, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, 801 South Paulina Street, Illinois 60612 (United States); Rodriguez, Anthony [Tissue Engineering Laboratory MC 841, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, 801 South Paulina Street, Illinois 60612 (United States); Hussain, Mohammad A. [Tissue Engineering Laboratory MC 841, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, 801 South Paulina Street, Illinois 60612 (United States); Mao, Jeremy J. [Tissue Engineering Laboratory MC 841, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, 801 South Paulina Street, Illinois 60612 (United States)]. E-mail: jmao2@uic.edu

    2007-04-15

    Bone-implant interface is characterized by an array of cells and macromolecules. This study investigated the nanomechancial properties of bone-implant interface using atomic force microscopy in vitro, and the mechanical modulation of implant bone ingrowth in vivo using bone histomorphometry. Upon harvest of screw-type titanium implants placed in vivo in the rabbit maxilla and proximal femur for 4 weeks, nanoindentation was performed in the bone-implant interface at 60-{mu}m intervals radially from the implant surface. The average Young's Moduli (E) of the maxillary bone-implant interface was 1.13 {+-} 0.27 MPa, lacking significant differences at all intervals. In contrast, an increasing gradient of E was observed radially from the femur bone-implant interface: 0.87 {+-} 0.25 MPa to 2.24 {+-} 0.69 MPa, representing significant differences among several 60-{mu}m intervals. In a separate experiment, bone healing was allowed for 6 weeks for proximal femur implants. The right femoral implant received axial cyclic loading at 200 mN and 1 Hz for 10 min/d over 12 days, whereas the left femoral implant served as control. Cyclic loading induced significantly higher bone volume, osteoblast numbers per endocortical bone surface, mineral apposition rate, and bone formation rate than controls. These data demonstrate nanoscale and microscale characterizations of bone-implant interface, and mechanical modulation of bone ingrowth surrounding titanium implants.

  7. Ovariectomy-induced changes in aged beagles: Histomorphometry and mineral content of the rib

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, A.K.; Bhattacharyya, M.H.; Hurst, D. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology; Miller, S. [Univ. of Utah, Salt Lake City, UT (United States). Radiobiology Div.; Sacco-Gibson, N. [Proctor and Gamble Pharmaceuticals, Cincinnati, OH (United States)

    1997-08-01

    The effects of ovariectomy on the aged beagle skeleton were studied by histomorphometric analysis of the cortical bone in sequential rib biopsies. Biopsies were taken from each ovariectomized (OV) or sham-operated (SO) dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) just prior to each postoperative biopsy to provide markers of bone formation. Analysis of sequential biopsies provided a means to follow the response to ovariectomy over time and compare each animal against its own baseline. Examination of sequential biopsies indicated that cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. Ovariectomy did not influence histomorphometric indices at one month after surgery, but substantial differences were observed at later times. Ovariectomy stimulated a transient increase in bone formation and was increased six-fold over that of SO dogs at four months. Ribs were also analyzed for mineral content at necropsy. The rib was heterogeneous along its length for calcium content and concentration. In the midrib where biopsies for histomorphometric analysis were taken, ovariectomy induced a decrease in mass and mineral content; total calcium was decreased by approximately 31%. These data demonstrate that the rib cortical bone is a responsive site for the effects of ovariectomy in female dogs.

  8. Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases.

    Science.gov (United States)

    Magni, Paolo; Macchi, Chiara; Sirtori, Cesare R; Corsi Romanelli, Massimiliano Marco

    2016-10-01

    Clear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic β-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research.

  9. Impairment of bone health in pediatric patients with hemolytic anemia.

    Directory of Open Access Journals (Sweden)

    Michael M Schündeln

    Full Text Available INTRODUCTION: Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. STUDY DESIGN: To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients. Biochemical, radiographic and anamnestic parameters of bone health were assessed. RESULTS: Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5% in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007. Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001. Multiple stepwise regression analysis revealed a significant (P<0.025 influence of LDH (partial r2 = 0.29, diagnosis of hemolytic anemia (partial r2 = 0.05 and age (partial r2 = 0.03 on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. CONCLUSION: Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment.

  10. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  11. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  12. Combinatorial effect of Si4+, Ca2+, and Mg2+ released from bioactive glasses on osteoblast osteocalcin expression and biomineralization.

    Science.gov (United States)

    Saffarian Tousi, Neda; Velten, Megen F; Bishop, Timothy J; Leong, Kelly K; Barkhordar, Nicole S; Marshall, Grayson W; Loomer, Peter M; Aswath, Pranesh B; Varanasi, Venu G

    2013-07-01

    Osteocalcin (OCN) expression is an essential osteogenic marker of successful bone regeneration therapies. This study hypothesizes that Si(4+) and Ca(2+) combinatorial released by bioactive glass enhance osteoblast biomineralization through up-regulation of OCN expression; and Mg(2+) release delays such enhancement. Osteoblasts (MC3T3-E1) were treated with ionic products of bioactive glass dissolution (6P53-b experimental bioactive glass and 45S5 commercial Bioglass™). Results showed that gene expressions, including OCN and its up-stream transcription factors (Runx2, ATF4, MSX1, SP7/OSX), growth factors and signaling proteins (BMP2, BMP6, SMAD3), were enhanced in both 45S5 and 6P53-b glass conditioned mediums (GCMs). This up-regulation led to enhanced mineral formation by 45S5 glass conditioned mediums ([GCM], Si(4+)+Ca(2+)) after 20 days, and by 45S5 GCM and 6P53-b GCM (Si(4+)+Ca(2+)+Mg(2+)) after 30 days. In examining the extracellular matrix generated by cells when exposed to each GCM, it was found that 45S5 GCM had slightly elevated levels of mineral content within ECM as compared to 6P53-b GCM after 30 days while control treatments exhibited no mineral content. The formation of well-defined mineralized nodules (distinct PO4(3-) [960 cm(-1)] and CO3(2-) [1072 cm(-1)] peaks from Raman Spectra) was observed for each GCM as the soluble glass content increased. In examining the individual and combined ion effects between Si(4+), Ca(2+), and Mg(2+), it was found Mg(2+) down-regulates OCN expression. Thus, ions released from both 45S5 and 6P53-b bioactive glasses up-regulate OCN expression and biomineralization while 6P53-b GCM Mg(2+) release down-regulated OCN expression and delayed osteoblast biomineralization. These results indicate that Si(4+), Ca(2+), and Mg(2+) combinatorially regulate osteoblast OCN expression and biomineralization. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found...... in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  14. The temporal response of bone to unloading

    Science.gov (United States)

    Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

    1984-01-01

    Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

  15. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

    OpenAIRE

    Schoon, E; Muller, M; Vermeer, C.; Schurgers, L; Brummer, R; Stockbrugger, R.

    2001-01-01

    BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine seru...

  16. [Secondary osteoporosis UPDATE. Bone metabolic change and osteoporosis during pregnancy and lactation].

    Science.gov (United States)

    Kurabayashi, Takumi; Tamura, Ryo; Hata, Yuki; Nishijima, Shota; Tsuneki, Ikunosuke; Tamura, Masaki; Yanase, Toru

    2010-05-01

    Calcium transfer from the mother to the infant during pregnancy and lactation plays an extremely important role in the bone health of the mother and neonate. Calcium aids in bone health through all ages but is especially crucial during pregnancy and lactation. Changes in the structure and metabolism of bone during pregnancy and the early stage of postpartum are evaluated by investigating bone mineral density (BMD), bone histomorphometry and bone markers of human or animal models. The bone resorption increased at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. Puerperal BMD remained static over the subsequent 5-10 years. If the women have a low BMD at this stage of their reproductive life, it tends not to improve over this time. Perhaps identification of this at-risk group may lead to effective interventions to reduce fracture risk in later life.

  17. Influence of orlistat on bone turnover and body composition

    DEFF Research Database (Denmark)

    Gotfredsen, A; Westergren Hendel, H; Andersen, T

    2001-01-01

    of bone mineral and body composition included total bone mineral content (TBMC), total bone mineral density (TBMD), lumbar spine BMC and BMD, forearm BMC and BMD, fat mass (FM), fat free-mass (FFM), percentage fat mass (FM%) as well as a DXA estimate of the body weight. Body composition (FM, FFM and FM...... biochemical variables except s-osteocalcin changed significantly after 1 y in the OLS group, disclosing a pattern of an incipient negative vitamin D balance, a secondary increase in PTH-secretion, and an increase in bone turnover with the emphasis on an increase in resorption parameters (fU-OHpr/creat, f...

  18. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    Science.gov (United States)

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  19. Vitamin K and bone health.

    Science.gov (United States)

    Hamidi, Maryam S; Gajic-Veljanoski, Olga; Cheung, Angela M

    2013-01-01

    Vitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women.

  20. Histomorphometry of the organic matrix of the femur in ovariectomized rats treated with sodium alendronate

    Directory of Open Access Journals (Sweden)

    Patricia Tanios Haddad

    2015-02-01

    Full Text Available OBJECTIVE: To evaluate the effect of two different concentrations of sodium alendronate on the quantity of organic matrix in the femur of rats with estrogen suppression caused by ovariectomy.METHODS: Sixty-days-old Wistar rats (Rattus norvegicus were subjected to bilateral laparotomy to remove the ovaries. The animals were divided into a control group, in which they only underwent laparotomy; an ovariectomized group (OVX; an ovariectomized group treated with 1 mg/kg of alendronate (OVX 1 mg; and an ovariectomized group treated with 2 mg/kg of alendronate (OVX 2 mg. The rats received alendronate twice a week for 90 days. The left femur was then removed, fixed and processed for embedding in paraffin. Semi-serial sections stained with hematoxylin and eosin were used to determine the area occupied by organic bone matrix, by means of image analysis software. The animals' weights were obtained at the beginning and end of the experiment.RESULTS: The ovariectomized animals and those treated with 1 mg/kg of alendronate presented significant increases in body weight (p 0.05 to that of the non-ovariectomized control animals (2,04,800 ± 9590, which indicates that this medication had a preventive effect with regard to bone mass loss.CONCLUSION: The higher concentration of the medication, administered twice a week for 90 days, was more effective than the dose of 1 mg/kg over the same period.

  1. Osteocalcin levels on oral glucose load in women being investigated for polycystic ovary syndrome.

    Science.gov (United States)

    Schwetz, Verena; Lerchbaum, Elisabeth; Schweighofer, Natascha; Hacker, Nicole; Trummer, Olivia; Borel, Olivier; Pieber, Thomas R; Chapurlat, Roland; Obermayer-Pietsch, Barbara

    2014-01-01

    Osteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit between the pancreas and osteoblasts. Effects of a 75-g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC), and carboxylated osteocalcin (cOC) in insulin-resistant (IR) and noninsulin-resistant (nIR) premenopausal women was evaluated, and the relationships of changes in OC, ucOC, and cOC with area under the curve (AUC) insulin and the Matsuda index were examined. In this cross-sectional study, 105 premenopausal women underwent OGTT; 18 were IR (homeostatic model assessment of insulin resistance [HOMA-IR] > 2.6; (2 with type 2 diabetes, 2 with impaired glucose tolerance), and 87 were nIR (3 with impaired glucose tolerance). Changes in total OC, ucOC, and cOC were evaluated 60 and 120 minutes after glucose loading. At baseline, IR subjects had significantly lower levels of total OC, cOC, and ucOC. In nIR women, total OC decreased by 19% from 18.0 ng/mL (14.5-24.7) at baseline to 14.6 ng/mL (10.9-17.8) after 120 minutes, ucOC decreased by 22% from 3.2 ng/mL (2.1-4.5) to 2.5 ng/mL (1.7-3.5), and cOC decreased by 26% from 14.9 ng/mL (12.1-20.4) to 11.1 ng/mL (9.0-14.5) (P < .001, respectively). No significant decreases were noted in IR subjects. The declines in OC and cOC predicted AUCinsulin (ΔOC: β = 0.301, P = .001; ΔcOC: β = 0.315, P < .001) and the Matsuda index (ΔOC: β = -0.235, P = .003; ΔcOC: β = -0.245, P = .002). Glucose intake lowers levels of OC, ucOC, and cOC in nIR women, the extent of which predicts IR and insulin sensitivity in premenopausal women. OC parameters seem suppressed in IR women. There might be a differential osteoblast response to oral glucose in IR and nIR women, with OC reflecting this finding.

  2. Osteocalcin and matrix GLA protein in developing teleost teeth: identification of sites of mRNA and protein accumulation at single cell resolution.

    Science.gov (United States)

    Ortiz-Delgado, J B; Simes, D C; Gavaia, P; Sarasquete, C; Cancela, M L

    2005-08-01

    In this study, the tissue distribution and accumulation of osteocalcin or bone Gla protein (BGP) and matrix Gla protein (MGP) were determined during tooth development in a teleost fish, Argyrosomus regius. In this species, the presence of BGP and MGP mRNA in teeth was revealed by in situ hybridization. mRNA for BGP was detected in the odontoblasts as well as in its cytoplasmic processes emerging through dentinal tubules, while mRNA for MGP was expressed in the enamel portion within the apical portion of the elongated cell bodies of enameloblasts, adjacent to the root of the teeth as well as in cells within the pulpal space. Immunolocalization of BGP and MGP demonstrated that these proteins accumulate mainly in the mineralized dentin or in enameloblastic processes, confirming in situ hybridization results. In this study, we examined for the first time the localization of both BGP and MGP gene expression and protein accumulation within the different regions of the vertebrate tooth. We clearly demonstrated that although the overall pattern of BGP and MGP gene expression and protein accumulation in A. regius teeth was in general agreement to what is known for other vertebrates such as rats or rodents, our study provided novel information and highlighted some species-differences between fish and higher vertebrates.

  3. Prostaglandin E2 Adds Bone to a Cancellous Bone Site with a Closed Growth Plate and Low Bone Turnover in Ovariectomized Rats

    Science.gov (United States)

    Ma, Y. F.; Ke, H. Z.; Jee, W. S. S.

    1994-01-01

    The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial metaphysis, PTM). Thirty-five 3-month old female Sprague-Dawley rats were divided into five groups: basal, sham-OVX, and OVX+0, +1, or +6 mg PGE2/kg/d injected subcutaneously for 3 months and given double fluorescent labels before sacrifice. Cancellous bone histomorphometric analyses were performed on 20-micron-thick undecalcified DTM sections. Similar to the PTM, the DTM showed age-related decreases in bone formation and increases in bone resorption, but it differed in that at 3 months post-OVX; there was neither bone loss nor changes in formation endpoints. Giving 1 mg PGE2/kg/d to OVX rats prevented most age-related changes and maintained the bone formation histomorphometry near basal levels. Treating OVX rats with 6 mg PGE2/kg/d prevented age-related bone changes, added extra bone, and improved microanatomical structure by stimulating bone formation without altering bone resorption. Furthermore, after PGE2 administration, the DTM, a cancellous bone site with a closed growth plate, inereased bone formation more than did the cancellous bone in the PTM.

  4. Relation between body composition and biochemical markers of bone turnover among early postmenopausal women

    DEFF Research Database (Denmark)

    Hla, M M; Davis, J W; Ross, P D

    2000-01-01

    , the mean levels of osteocalcin decreased by 3% and 13%, respectively; NTX decreased by 5 and 21%. Fat mass and whole-body BMC were also significantly associated with decreases in the average of osteocalcin and NTX Z-scores. By contrast, the mean levels of serum osteocalcin increased by 2 and 11......%, respectively, per IQR increase in muscle strength and height; NTX increased by 4 (not significant) and 14%, respectively. Both muscle strength and height were significantly associated with increases in the average Z-scores. These exploratory analyses suggest that fat mass and whole-body BMC were associated...... with decreased bone turnover, while muscle strength and height were associated with increased bone turnover....

  5. Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial

    DEFF Research Database (Denmark)

    Rasmussen, Thomas A; Jensen, Danny; Tolstrup, Martin;

    2012-01-01

    Introduction Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy. Methods In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT....../3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx...

  6. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    Science.gov (United States)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  7. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    Science.gov (United States)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  8. Alteration of proteoglycan sulfation affects bone growth and remodeling.

    Science.gov (United States)

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-05-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. No effect of platelet-rich plasma with frozen or processed bone allograft around noncemented implants

    DEFF Research Database (Denmark)

    Jensen, T B; Rahbek, O; Overgaard, S

    2005-01-01

    We compared processed morselized bone allograft with fresh-frozen bone graft around noncemented titanium implants. Also, the influence of platelet-rich plasma (PRP) in combination with bone allograft was evaluated. Analysis was based on implant fixation and histomorphometry. PRP was prepared...... by isolating the buffy coat from autologous blood samples. Bone allograft was used fresh-frozen or processed by defatting, freeze drying, and irradiation. Cylindrical hydroxyapatite-coated titanium implants were inserted bilaterally in the femoral condyles of eight dogs. Each implant was surrounded by a 2.5-mm...... concentric gap, which was filled randomly according to the four treatment groups--group 1: fresh-frozen bone allograft; group 2: processed bone allograft; group 3: fresh-frozen bone allograft + PRP; group 4: processed bone allograft + PRP. Histological and mechanical evaluation demonstrated no influence...

  10. Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia

    Science.gov (United States)

    Batista, Marco Antonio; Leivas, Tomaz Puga; Rodrigues, Consuelo Junqueira; Arenas, Géssica Cantadori Funes; Belitardo, Donizeti Rodrigues; Guarniero, Roberto

    2011-01-01

    OBJECTIVE: To perform a comparative analysis of the effects of platelet-rich plasma and centrifuged bone marrow aspirate on the induction of bone healing in rabbits. METHOD: Twenty adult, male New Zealand rabbits were randomly separated into two equal groups, and surgery was performed to create a bone defect (a cortical orifice 3.3 mm in diameter) in the proximal metaphysis of each rabbit's right tibia. In the first group, platelet-rich plasma was implanted in combination with β-tricalcium phosphate (platelet-rich plasma group), and in the second group, centrifuged bone marrow in combination with β-tricalcium phosphate (centrifuged bone marrow group) was implanted. After a period of four weeks, the animals were euthanized, and the tibias were evaluated using digital radiography, computed tomography, and histomorphometry. RESULTS: Seven samples from each group were evaluated. The radiographic evaluation confirmed the absence of fractures in the postoperative limb and identified whether bone consolidation had occurred. The tomographic evaluation revealed a greater amount of consolidation and the formation of a greater cortical bone thickness in the platelet-rich plasma group. The histomorphometry revealed a greater bone density in the platelet-rich plasma group compared with the centrifuged bone marrow group. CONCLUSION: After four weeks, the platelet-rich plasma promoted a greater amount of bone consolidation than the bone marrow aspirate concentrate. PMID:22012052

  11. Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia

    Directory of Open Access Journals (Sweden)

    Marco Antonio Batista

    2011-01-01

    Full Text Available OBJECTIVE: To perform a comparative analysis of the effects of platelet-rich plasma and centrifuged bone marrow aspirate on the induction of bone healing in rabbits. METHOD: Twenty adult, male New Zealand rabbits were randomly separated into two equal groups, and surgery was performed to create a bone defect (a cortical orifice 3.3 mm in diameter in the proximal metaphysis of each rabbit's right tibia. In the first group, platelet-rich plasma was implanted in combination with β-tricalcium phosphate (platelet-rich plasma group, and in the second group, centrifuged bone marrow in combination with β-tricalcium phosphate (centrifuged bone marrow group was implanted. After a period of four weeks, the animals were euthanized, and the tibias were evaluated using digital radiography, computed tomography, and histomorphometry. RESULTS: Seven samples from each group were evaluated. The radiographic evaluation confirmed the absence of fractures in the postoperative limb and identified whether bone consolidation had occurred. The tomographic evaluation revealed a greater amount of consolidation and the formation of a greater cortical bone thickness in the platelet-rich plasma group. The histomorphometry revealed a greater bone density in the platelet-rich plasma group compared with the centrifuged bone marrow group. CONCLUSION: After four weeks, the platelet-rich plasma promoted a greater amount of bone consolidation than the bone marrow aspirate concentrate.

  12. Evaluation of serum undercarboxylated osteocalcin in premenopausal rheumatoid arthritis patients: its correlation with disease activity and bone mineral density

    Directory of Open Access Journals (Sweden)

    Heba A Esaily

    2016-01-01

    Conclusion Serum level of ucOC (which is a mirror of vitamin K deficiency was found to be higher in premenopausal RA patients than controls and correlated positively with disease activity and inversely with BMD measurement.

  13. Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome

    OpenAIRE

    2001-01-01

    The Saethre-Chotzen syndrome is characterized by premature fusion of cranial sutures resulting from mutations in Twist, a basic helix-loop-helix (bHLH) transcription factor. We have identified Twist target genes using human mutant calvaria osteoblastic cells from a child with Saethre-Chotzen syndrome with a Twist mutation that introduces a stop codon upstream of the bHLH domain. We observed that Twist mRNA and protein levels were reduced in mutant cells and that the Twist mutation increased c...

  14. Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight.

    Science.gov (United States)

    Knapen, Marjo H J; Schurgers, Leon J; Shearer, Martin J; Newman, Paul; Theuwissen, Elke; Vermeer, Cees

    2012-09-28

    Osteocalcin (OC) is a vitamin K-dependent protein found in bone and in circulation. High serum γ-carboxylated OC reflects a high, and high uncarboxylated OC (ucOC) reflects a low vitamin K status. A revolutionary hypothesis is that ucOC acts as a hormone improving glucose handling and reducing fat mass. The objective was to test the logical extrapolation of the ucOC hormone hypothesis to humans that elevated ucOC is associated with higher body weight, BMI and fat mass. In a cross-sectional analysis, the associations of vitamin K status with circulating adiponectin and body composition were investigated in 244 postmenopausal women (study I). The effects of vitamin K treatment on adiponectin, body weight and BMI were investigated in archived samples from forty-two young men and women who received varying doses of menaquinone-7 during 12 weeks (study II) and from a cohort of 164 postmenopausal women who participated in a 3-year placebo-controlled trial on 45 mg menaquinone-4 (MK-4) (study III). No association was found between vitamin K status and circulating adiponectin before or after vitamin K supplementation. A higher carboxylation of OC was significantly correlated with lower body weight, BMI and fat mass of the trunk. Women taking MK-4 maintained their baseline body weight and BMI, whereas women taking placebo showed significant increases in both indices. These findings demonstrate that a high vitamin K status of bone has no effect on circulating adiponectin in healthy people and long-term vitamin K supplementation does not increase weight in healthy postmenopausal women.

  15. Unique local bone tissue characteristics in iliac crest bone biopsy from adolescent idiopathic scoliosis with severe spinal deformity

    Science.gov (United States)

    Wang, Zhiwei; Chen, Huanxiong; Yu, Y. Eric; Zhang, Jiajun; Cheuk, Ka-Yee; Ng, Bobby K. W.; Qiu, Yong; Guo, X. Edward; Cheng, Jack C. Y.; Lee, Wayne Y. W.

    2017-01-01

    Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS. PMID:28054655

  16. The effect of enterocystoplasty on bone strength assessed at four different skeletal sites in a rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Mosekilde, Li.; Thomsen, J.S.

    2003-01-01

    ; colocystoplasty; or sham operation (controls). After 8 months the lumbar vertebrae, femora, and tibiae were harvested at necropsy. Bone strength was assessed biomechanically at four different skeletal sites: vertebra L3, femoral middiaphysis, femoral neck, and distal femoral metaphysis. Bone mass and architecture...... were assessed using standard static histomorphometry of the proximal tibial metaphysis (trabecular bone volume [BV/TV]; trabecular number [Tb.N]) and ash weight. Statistically significant differences of biomechanical parameters between groups were observed at three skeletal sites with corresponding......, this is the first experimental study to demonstrate the relevance of histomorphometrically proven bone loss after enterocystoplasty in terms of biomechanical variables....

  17. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Bleil, Janine; Maier, Rene;

    2016-01-01

    . Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling...

  18. Effects of vitamin K on the morphometric and material properties of bone in the tibiae of growing rats.

    Science.gov (United States)

    Matsumoto, Takeshi; Miyakawa, Takushi; Yamamoto, Daiki

    2012-03-01

    Suboptimal vitamin K nutriture is evident during rapid growth. We aimed to determine whether vitamin K(2) (menaquinone-4 [MK-4]) supplementation is beneficial to bone structure and intrinsic bone tissue properties in growing rats. Male Wistar rats (5 weeks old) were assigned to either a control diet (n = 8) or an MK-4-supplemented diet (22 mg d(-1) kg(-1) body weight, n = 8). After a 9-week feeding period, we determined the serum concentration ratio of undercarboxylated osteocalcin to γ-carboxylated osteocalcin and the urinary deoxypyridinoline level. All rats were then euthanized, and their tibiae were analyzed by micro-computed tomography for trabecular architecture and synchrotron radiation micro-computed tomography for cortical pore structure and mineralization. Fourier transform infrared microspectroscopy and a nanoindentation test were performed on the cortical midlayers of the anterior and posterior cortices to assess bone tissue properties. Neither body weight nor tibia length differed significantly between the 2 groups. Dietary MK-4 supplementation decreased the ratio of undercarboxylated osteocalcin to γ-carboxylated osteocalcin but did not affect deoxypyridinoline, indicating a positive effect on bone formation but not bone resorption. Trabecular volume fraction and thickness were increased by MK-4 (P < .05). Neither the cortical pore structure nor mineralization was affected by MK-4. On the other hand, MK-4 increased mineral crystallinity, collagen maturity, and hardness in both the anterior and posterior cortices (P < .05). These data indicate the potential benefit of MK-4 supplementation during growth in terms of enhancing bone quality.

  19. Bone response to fluoride exposure is influenced by genetics.

    Directory of Open Access Journals (Sweden)

    Cláudia A N Kobayashi

    Full Text Available Genetic factors influence the effects of fluoride (F on amelogenesis and bone homeostasis but the underlying molecular mechanisms remain undefined. A label-free proteomics approach was employed to identify and evaluate changes in bone protein expression in two mouse strains having different susceptibilities to develop dental fluorosis and to alter bone quality. In vivo bone formation and histomorphometry after F intake were also evaluated and related to the proteome. Resistant 129P3/J and susceptible A/J mice were assigned to three groups given low-F food and water containing 0, 10 or 50 ppmF for 8 weeks. Plasma was evaluated for alkaline phosphatase activity. Femurs, tibiae and lumbar vertebrae were evaluated using micro-CT analysis and mineral apposition rate (MAR was measured in cortical bone. For quantitative proteomic analysis, bone proteins were extracted and analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS, followed by label-free semi-quantitative differential expression analysis. Alterations in several bone proteins were found among the F treatment groups within each mouse strain and between the strains for each F treatment group (ratio ≥1.5 or ≤0.5; p<0.05. Although F treatment had no significant effects on BMD or bone histomorphometry in either strain, MAR was higher in the 50 ppmF 129P3/J mice than in the 50 ppmF A/J mice treated with 50 ppmF showing that F increased bone formation in a strain-specific manner. Also, F exposure was associated with dose-specific and strain-specific alterations in expression of proteins involved in osteogenesis and osteoclastogenesis. In conclusion, our findings confirm a genetic influence in bone response to F exposure and point to several proteins that may act as targets for the differential F responses in this tissue.

  20. Occlusal effects on longitudinal bone alterations of the temporomandibular joint.

    Science.gov (United States)

    Zhang, J; Jiao, K; Zhang, M; Zhou, T; Liu, X-D; Yu, S-B; Lu, L; Jing, L; Yang, T; Zhang, Y; Chen, D; Wang, M-Q

    2013-03-01

    The pathological changes of subchondral bone during osteoarthritis (OA) development in the temporomandibular joint (TMJ) are poorly understood. In the present study, we investigated the longitudinal alterations of subchondral bone using a rat TMJ-OA model developed in our laboratory. Changes in bone mass were examined by micro-CT, and changes in osteoblast and osteoclast activities were analyzed by real-time PCR, immunohistochemistry, and TRAP staining. Subchondral bone loss was detected from 8 weeks after dental occlusion alteration and reached the maximum at 12 weeks, followed by a repair phase until 32 weeks. Although bone mass increased at late stages, poor mechanical structure and lower bone mineral density (BMD) were found in these rats. The numbers of TRAP-positive cells were increased at 12 weeks, while the numbers of osteocalcin-expressing cells were increased at both 12 and 32 weeks. Levels of mRNA expression of TRAP and cathepsin K were increased at 12 weeks, while levels of ALP and osteocalcin were increased at both 12 and 32 weeks. These findings demonstrated that there is an active bone remodeling in subchondral bone in TMJs in response to alteration in occlusion, although new bone was formed with lower BMD and poor mechanical properties.

  1. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  2. Three-dimensional quantification of structures in trabecular bone using measures of complexity.

    Science.gov (United States)

    Marwan, Norbert; Kurths, Jürgen; Thomsen, Jesper Skovhus; Felsenberg, Dieter; Saparin, Peter

    2009-02-01

    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-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 (microCT) from human proximal tibiae and lumbar vertebrae at different stages of osteoporotic bone loss. The outcome is compared to the results of conventional static histomorphometry and exhibits clear relationships between the analyzed geometrical features of trabecular bone and loss of bone density, but also indicate that the measures reveal additional information about the structural composition of bone, which were not revealed by the static histomorphometry. Finally, we have studied the dependency of the developed measures of complexity on the spatial resolution of the microCT data sets.

  3. Targeting Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone

    Science.gov (United States)

    2013-01-01

    Coffin-Lowry Syndrome. Cell 117, 387–398 20. Hauschka, P. V. (1986) Osteocalcin: the vitamin K-dependent Ca2-bind- ing protein of bone matrix...cellular biology of intermediate filaments. Annu. Rev. Biochem. 57, 593–625 26. Wu, Y., Zhang, X., Salmon ,M., Lin, X., and Zehner, Z. E. (2007

  4. Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus.

    Science.gov (United States)

    Lappin, David F; Eapen, Bob; Robertson, Douglas; Young, Jenny; Hodge, Penny J

    2009-08-01

    To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. Plasma concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes.

  5. Sperm Quality and Testicular Histomorphometry of Wistar Rats Supplemented with Extract and Fractions of Fruit of Tribulus terrestris L.

    Directory of Open Access Journals (Sweden)

    Nelma Neylanne Pinho Muniz Oliveira

    2015-12-01

    Full Text Available ABSTRACT The aim of this study was to assess the sperm quality and testicular histomorphometry of Wistar rats supplemented with extract and fractions of fruits of Tribulus terrestris L. The ethanolic extract was obtained by dynamic maceration of spray-dried fruit. This extract was fractionated by liquid-liquid partition, using increasing polarity solvents. Twenty male rats were separated in four groups, with five rats in each group. The control was supplemented with distilled water, while the others were daily given the ethanolic extract, hexanic or aqueous fraction soluble in methanol in a dose of 42 mg.kg-1.day-1 for 70 days. Sperm was obtained from the right epididymal tail for the analysis of motility, count, morphology and viability. The testicular weight of groups supplemented with ethanolic extract and aqueous fraction soluble in methanol was higher when compared to the control. The gonadosomatic index increased in the group supplemented with ethanolic extract. The nuclear, cytoplasmic and individual volume of Leydig cells increased in supplementation with hexanic and aqueous fractions soluble in methanol. It was concluded that the extract influenced the spermatogenesis, while hexanic and aqueous fractions soluble in methanol promoted the changes in the intertubular compartment. Therefore, Tribulus terrestris did not improve the sperm quality of the rats.

  6. Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.

    Science.gov (United States)

    Jiao, K; Niu, L; Xu, X; Liu, Y; Li, X; Tay, F R; Wang, M

    2015-06-01

    Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

  7. Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats.

    Science.gov (United States)

    Shen, Chwan-Li; Cao, Jay J; Dagda, Raul Y; Tenner, Thomas E; Chyu, Ming-Chien; Yeh, James K

    2011-06-01

    Recent studies show that green tea polyphenols (GTPs) attenuate bone loss and microstructure deterioration in ovariectomized aged female rats, a model of postmenopausal osteoporosis. This study evaluated the efficacy of GTPs at mitigating bone loss and microstructure deterioration along with related mechanisms in androgen-deficient aged rats, a model of male osteoporosis. A 2 (sham vs. orchidectomy) × 2 (no GTP and 0.5% GTP in drinking water) factorial design was studied for 16 weeks using 40 aged male rats. An additional 10 rats (baseline group) were killed at the beginning of study to provide baseline parameters. There was no difference in femoral mineral density between baseline and the sham only group. Orchidectomy suppressed serum testosterone and tartrate-resistant acid phosphatase concentrations, liver glutathione peroxidase activity, bone mineral density, and bone strength. Orchidectomy also decreased trabecular bone volume, number, and thickness in the distal femur and proximal tibia and bone-formation rate in trabecular bone of proximal tibia but increased serum osteocalcin concentrations and bone-formation rates in the endocortical tibial shaft. GTP supplementation resulted in increased serum osteocalcin concentrations, bone mineral density, and trabecular volume, number, and strength of femur; increased trabecular volume and thickness and bone formation in both the proximal tibia and periosteal tibial shaft; decreased eroded surface in the proximal tibia and endocortical tibial shaft; and increased liver glutathione peroxidase activity. We conclude that GTP supplementation attenuates trabecular and cortical bone loss through increasing bone formation while suppressing bone resorption due to its antioxidant capacity.

  8. Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Gao Shu-guang

    2012-06-01

    Full Text Available Abstract Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF. However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC, bone mineral density (BMD, bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption, affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface, and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

  9. Guided bone regeneration is promoted by the molecular events in the membrane compartment.

    Science.gov (United States)

    Turri, Alberto; Elgali, Ibrahim; Vazirisani, Forugh; Johansson, Anna; Emanuelsson, Lena; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-04-01

    The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier.

  10. Is bone transplantation the gold standard for repair of alveolar bone defects?

    Directory of Open Access Journals (Sweden)

    Cassio Eduardo Raposo-Amaral

    2014-01-01

    Full Text Available New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate, compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7 defects were repaired with autogenous bone grafts; Group 2 (n = 5 defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5 defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5 defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6 defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2–5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01 and 38.35% ± 19.59% (p = 0.06 of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30 and 61.80% ± 2.14% (p = 0.88 of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

  11. Is bone transplantation the gold standard for repair of alveolar bone defects?

    Science.gov (United States)

    Raposo-Amaral, Cassio Eduardo; Bueno, Daniela Franco; Almeida, Ana Beatriz; Jorgetti, Vanda; Costa, Cristiane Cabral; Gouveia, Cecília Helena; Vulcano, Luiz Carlos; Fanganiello, Roberto D; Passos-Bueno, Maria Rita

    2014-01-01

    New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate), compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7) defects were repaired with autogenous bone grafts; Group 2 (n = 5) defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5) defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5) defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6) defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2–5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01) and 38.35% ± 19.59% (p = 0.06) of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30) and 61.80% ± 2.14% (p = 0.88) of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone. PMID:24551445

  12. Bone morphogenetic protein-2-encapsulated grafted-poly-lactic acid-polycaprolactone nanoparticles promote bone repair.

    Science.gov (United States)

    Xu, Xiaojun; Yang, Jun; Ding, Lifeng; Li, Jianjun

    2015-01-01

    The aim of this study is to test the efficacy of a novel tissue-engineered bone in repairing bone defects, using poly-lactic-acid-polycaprolactone (PLA-PCL) scaffolding seeded with PEG-bone morphogenetic protein-2 (BMP-2)-transfected rBMSCs (rabbit bone marrow stromal cells). The rBMSCs were transfected with PEG/BMP-2 or liposome/BMP-2, and then implanted into a PLA-PCL tissue-engineered bone. The protein level of BMP-2 was assessed by Western blot analysis and immunohistochemistry. ELISA was used to measure the amount of BMP-2 secreted in the culture media. The mRNA level of BMP-2 and osteocalcin was assayed quantitatively by real-time PCR. The middle portion of the bilateral radius in New Zealand rabbits was excised and implanted with tissue-engineered bone, and the modified areas were monitored by X-ray, hematoxylin-eosin staining, and immunohistochemistry staining of BMP-2. PEG-BMP-2 nanoparticles (NPs) and BMP-2-loaded PEG-PLA-PCL tissue-engineered bones were successfully constructed. The novel PEG-PLA-PCL NPs/DNA complex was a superior option for transfecting BMP-2 in rBMSCs compared to normal liposomes Moreover, the mRNA level of osteocalcin and alkaline phosphatase activity was also elevated upon transfection of BMP-2-encapsulated NPs. In vivo implants with BMP-2-carried tissue-engineered bone exhibited dramatic augmentation of BMP-2 and effective bone formation in the rabbit ectopic model. The PEG-PLA-PCL NPs/BMP-2 complex had an advantageous effect on bone repair, which provided an important theoretic basis for potential clinical treatments.

  13. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  14. Genetic and environmental factors affecting peak bone mass in premenopausal Japanese women

    OpenAIRE

    Hayakawa, Yoshika; Yanagi, Hisako; Hara, Shuichi; Amagai, Hitoshi; Endo, Kazue; Hamaguchi, Hideo; Tomura, Shigeo

    2001-01-01

    The purpose of this study was to examine the relationships between peak bone mass and genetic and environmental factors. We measured whole-body bone mineral density (BMD), lumbar spine BMD, and radius BMD with dual-energy X-ray absorptiometry (DXA) and analyzed eight genetic factors: vitamin D receptor (VDR)-3′, VDR-5′, estrogen receptor (ER), calcitonin receptor (CTR), parathyroid hormone (PTH), osteocalcin (OC), apolipoprotein E (ApoE), and fatty acid binding protein 2 (FABP2) allelic polym...

  15. Effect of icariin and genistein on bone protection%淫羊藿苷与金雀异黄酮骨保护作用的比较研究

    Institute of Scientific and Technical Information of China (English)

    成魁; 陈克明; 葛宝丰; 甄平; 马慧萍; 高玉海

    2014-01-01

    Aim To compare the pharmacological ac-tivity of icariin( ICA) and genistien ( GEN) against os-teoporosis after oral administration with them to growing rats and ovariectomized rats. Methods 25 mg·kg-1 icariin and 10 mg · kg-1 genistein ( equal in molar concentration) were administered to one-month-old fe-male SD rats every day for three months. Treatments at the same dosage were administered to the 6-month-old ovariectomized SD rats every day for three months. Their effects were compared on bone mineral density and biomechanical properties of femurs and vertebrae, serum levels of osteocalcin and tartaric acid phospha-tase 5b ( TRACP 5b) and histomorphometry. Results The results showed that, in young rats, icariin treat-ment significantly increased bone mineral density, the maximum mechanical loads of femurs and vertebrae as well as the bone qualities ( serum markers and microar-chitecture ) , whereas genistein treatment had little effects compared with the non-treatment control. How-ever, genistein treatment was more efficacious than icariin in preventing bone loss and deterioration of bone microarchitecture in ovariectomized rats. Conclusion Our data suggest that, since icariin has a higher os-teogenic activity but lower estrogenic activity, it has been found to be more efficacious than genistein in peak bone mass accrual only in young rats. In the ovariectimized rats, however, as the main force to pre-vent bone loss is the estrogenic activity, genistein has been found to be more efficacious than icariin in reduc-ing bone loss.%目的通过淫羊藿苷( icariin, ICA)和金雀异黄酮( genistein, GEN)对幼龄大鼠和切除卵巢大鼠的药物干预,比较其抗骨质疏松的药理活性。方法1月龄意 SD大鼠灌服25 mg·kg-1·d-1淫羊藿苷和10 mg·kg-1·d-1金雀异黄酮3个月,6月龄SD切除卵巢大鼠灌服同样的剂量3个月,检测骨密度、股骨生物力学、血清骨钙素与抗酒石酸性磷酸酶5b和骨组织形态

  16. Transient intermittent hypoxia exposure disrupts neonatal bone strength

    Directory of Open Access Journals (Sweden)

    Gyuyoup eKim

    2016-03-01

    Full Text Available A brief intermittent hypoxia (IH, ambient O2 levels alternating between room air and 12% O2 for 1h immediately after birth resulted in pancreatic islet dysfunction associated with zinc deficiency as previously reported. We hypothesized that IH exposure modulates zinc homeostasis in bone as well, which leads to increased bone fragility. To test this hypothesis, we used neonatal rats and human osteoblasts. To examine IH-influences on osteoblasts devoid of neural influences, we quantified amounts of alkaline phosphatase and mineralization in IH-treated human osteoblasts. Bones harvested from IH-treated animals showed significantly reduced hardness and elasticity. The IH group also showed discretely decreased levels of alkaline phosphatase and mineralization amounts. The IH group showed a decreased expression of ZIP8 or Zrt and Irt-like protein 8 (a zinc uptake transporter, Runx2 (or Runt-related transcription factor 2, a master protein in bone formation, Collagen-1 (a major protein comprising the extracellular matrix of the bone, osteocalcin, and zinc content. When zinc was eliminated from the media containing human osteoblasts using a zinc chelate, and added later with zinc sulfate, Runx2, ZIP8 and osteocalcin expression decreased first, and recovered with zinc supplementation. Adenovirus-mediated ZIP8 over-expression in osteoblasts increased mineralization significantly as well. We conclude that IH impairs zinc homeostasis in bones and osteoblasts, and that such disturbances decrease bone strength, which can be recovered by zinc supplementation.

  17. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Andreasen, Christina Møller; Dencker, Mads L.;

    2015-01-01

    hydroxyapatite (ABM/P-15); hydroxyapatite + βtricalciumphosphate+ Poly-Lactic-Acid (HA/βTCP-PDLLA); or ABM/P-15+HA/βTCP-PDLLA. After nine weeks, bone-implant blocks were harvested and sectioned for micro-CT scanning, push-out test, and histomorphometry. Significant bone formation and implant fixation could...... implant were not significantly different among the four groups. The ABM/P-15 group had similar shear mechanical properties on implant fixation as the allograft group. Adding HA/βTCP-PDLLA to ABM/P-15 did not significantly change these parameters. This study revealed that ABM/P-15 had significantly bone...

  18. Bioreactor activated graft material for early implant fixation in bone

    DEFF Research Database (Denmark)

    Snoek Henriksen, Susan; Ding, Ming; Overgaard, Søren

    2011-01-01

    . The superficial part was used for mechanical testing and micro-CT scanning, and the profound part for histomorphometry. Push-out tests were performed on an 858 Bionix MTS hydraulic materials testing machine (MTS Systems Corporation, USA). Shear mechanical properties between implant and newly generated bone were......: No significant differences regarding failure energy (kJ/m2, p=0.44) or ultimate shear strength (MPa, p=0.17) could be seen. Shear stiffness (MPa) was significantly higher for the allograft group (p=0.04). Group 2: No significant differences regarding failure energy (p=0.11) or shear stiffness (p=0.52) could...

  19. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.

    Science.gov (United States)

    Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

    2014-03-01

    Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number.

  20. Effect of La3+ on osteoblastic differentiation of rat bone marrow stromal cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In the present work, the effect of La3+ on osteoblastic differentiation of primary rat bone marrow stromal cells (MSCs) as well as the related mechanisms are studied. Differentiation is monitored by detection of alkaline phosphatase (ALP) activity, osteocalcin secretion, the mRNA levels of Type I collagen and osteocalcin, and matrix mineralization. The results show that La3+ inhibits osteoblastic differentiation of MSCs in the early and middle stages of culture, as demonstrated by the decrease of ALP activity, osteocalcin secretion, and down-regulation of the mRNA level of osteocalcin. However, La3+ does not affect the matrix mineralization in advanced MSCs, because it up-regulates the mRNA levels of Type I collagen, and promotes ALP activity and osteocalcin secretion in MSCs in the late stage of culture. In addition, Western blot analysis exhibits that La3+ induces the phosphorylation and activation of mitogen-activated protein kinase (MAPK). Furthermore, MAPK kinase inhibitor PD98059 completely blocks the inhibitory effect of La3+ on ALP activity of MSCs in the middle stage of culture. These results suggest that La3+ affects MSCs osteoblastic differentiation depending on differentiation stages. La3+ inhibits osteoblastic differentiation of MSCs in the early and middle stages by a MAPK-dependent mechanism, but does not affect the matrix mineralization in advanced MSCs.

  1. Disuse exaggerates the detrimental effects of alcohol on cortical bone

    Science.gov (United States)

    Hefferan, Theresa E.; Kennedy, Angela M.; Evans, Glenda L.; Turner, Russell T.

    2003-01-01

    BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

  2. A MULTI-SITE SHEEP MODEL FOR CANCELLOUS BONE HEALING

    Directory of Open Access Journals (Sweden)

    Angad eMalhotra

    2014-09-01

    Full Text Available Appropriate, well characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14mm of fixed depth (25mm were compared in both skeletally immature (18 month old and aged sheep (5 year old. In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at four weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using µCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects, with woven bone normally forming near the periphery of the defect. Bone volume fraction (BV/TV significantly decreased with an increasing defect diameter. Actual bone volume (BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal, and encourages a reduction in animal numbers required for preclinical research.

  3. Modulation of Isoflavones on Bone-nodule Formation in Rat Calvaria Osteoblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To observe the effects of two main isoflavones, daidzein and genistein on the bone-nodule formation in rat calvaria osteoblasts in vitro. Methods Osteoblasts obtained from newborn Sprague-dawley rat calvarias were cultured for several generations. The second generation cells were cultured in Minimum Essential Medium supplemented with ascorbic acid and Na-beta-glycerophosphate for several days, in the presence of daidzein and genistein, with or without the estrogen receptor antagonist ICI 182780. Number of nodules was counted at the end of the incubation period (day 20) by staining with Alizarin Red S calcium stain. The release of osteocalcin, as a marker of osteoblast activity, was also determined on day 7 and day 12 during the incubation period. Results Compared with the control, the numbers of nodules were both increased by incubation with daidzein and genistein. 17a-estradiol was used as a positive control and proved to be a more effective inducer of the increase in bone-nodules formation than daidzein and genistein. The release of osteocalcin into culture media was also increased in the presence of daidzein and genistein, as well as 17a-estradiol on day 7 and day 12 (day 12 were higher). The estrogen receptor antagonist ICI 182780 completely blocked the genistein- and 17a-estradiol-induced increase of nodule numbers and osteocalcin release in osteoblasts. However, the effects induced by daidzein could not be inhibited by ICI 182780. Conclusion These findings suggest that geinistein can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts. The effects, like those induced by 17a-estradiol, are mediated by the estrogen receptor dependent pathway. Daidzein also can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts, but it is not, at least not merely, mediated by the estrogen receptor dependent pathway.

  4. Bone mass and bone quality are altered by hypoactivity in the chicken.

    Directory of Open Access Journals (Sweden)

    Eric Aguado

    Full Text Available Disuse induces a rapid bone loss in adults; sedentarity is now recognized as a risk factor for osteoporosis. Hypoactivity or confinement also decrease bone mass in adults but their effects are largely unknown and only few animal models have been described. We have used 10 chickens of the rapidly growing strain 857K bred in a large enclosure (FREE group; 10 others were confined in small cages with little space to move around (HYPO group. They were sacrificed at 53 days and femurs and tibias were evaluated by texture analysis, dual energy X-ray densitometry, microcomputed tomography (microCT and histomorphometry. Hypoactivity had no effect on the length and diameter of the bones. Bone mineral density (BMD, microCT (trabecular bone volume and trabecular microarchitecture and texture analysis were always found significantly reduced in the animals of the HYPO group. BMD was reduced at both femur and tibia diaphysises; BMD of the metaphysis was significantly reduced in the femur but not in the tibia. An increase in osteoid volume and surfaces was noted in the HYPO group. However, there was no alteration of the mineral phase as the osteoid thickness did not differ from control animals. Bone loss was much more pronounced at the lower femur metaphysis than at the upper metaphysis of the tibia. At the tibia, only microarchitectural changes of trabecular bone could be evidenced. The confined chicken represents a new method for the study of hypodynamia since these animals do not have surgical lesions.

  5. The role of muscle loading on bone (Remodeling at the developing enthesis.

    Directory of Open Access Journals (Sweden)

    Alexander M Tatara

    Full Text Available Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (remodeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral shoulders injected with saline and a separate group of normal mice. It was hypothesized that muscle unloading would suppress bone formation and enhance bone resorption at the enthesis, and that the unloading-induced bony defects could be rescued by suppressing osteoclast activity. In order to modulate osteoclast activity, mice were injected with the bisphosphonate alendronate. Bone formation was measured at the tendon enthesis using alizarin and calcein fluorescent labeling of bone surfaces followed by quantitative histomorphometry of histologic sections. Bone volume and architecture was measured using micro computed tomography. Osteoclast surface was determined via quantitative histomorphometry of tartrate resistant acid phosphatase stained histologic sections. Muscle unloading resulted in delayed initiation of endochondral ossification at the enthesis, but did not impair bone formation rate. Unloading led to severe defects in bone volume and trabecular bone architecture. These defects were partially rescued by suppression of osteoclast activity through alendronate treatment, and the effect of alendronate was dose dependent. Similarly, bone formation rate was increased with increasing alendronate dose across loading groups. The bony defects caused by unloading were therefore likely due to maintained high osteoclast activity, which normally decreases from neonatal through mature timepoints. These results have important implications for the treatment of

  6. Serum under-carboxylated osteocalcin levels in women with polycystic ovary syndrome: weight-dependent relationships with endocrine and metabolic traits

    Directory of Open Access Journals (Sweden)

    Pepene Carmen E

    2013-01-01

    Full Text Available Abstract Background Under-carboxylated osteocalcin (ucOC, the precursor substrate of bone biomarker OC is a potent regulator of energy metabolism by promoting insulin production and adiponectin synthesis and decreasing fat stores. The aim of the present study was to point out the potential role of ucOC in the physiopathology of polycystic ovary syndrome (PCOS, a common disorder defined by the constellation of anovulation, insulinresistance, hyperinsulinemia, obesity and androgen excess. Methods In this prospective case–control investigation, 78 young premenopausal women, i.e. 52 PCOS patients and 26 age- and body mass index (BMI-matched healthy controls, were successively enrolled. Recruitment of PCOS patients was performed according to Androgen Excess-Polycystic Ovary Syndrome (AE-PCOS Society 2006 criteria. All study participants were subjected to clinical examination, whole-body composition assessment and measurements of serum ucOC, OC (1-49, glucose and lipids, insulin, total testosterone (TT, estradiol, sex-hormone binding globulin (SHBG, high-sensitivity C-reactive protein (Hs-CRP and β-CrossLaps. Results BMI-stratified multivariate analysis revealed significantly higher ucOC levels in PCOS vs. controls in lean (p = 0.001 but not overweight and obese study participants (p = 0.456. Notably, a positive correlation between ucOC and TT (p = 0.018, calculated free testosterone (cFT, p = 0.028 and serum insulin (p = 0.036, respectively, was found to be confined to the lean analysis subgroup. Furthermore, in stepwise multiple regression models, β-CrossLaps and cFT were able to predict 46.71% of serum ucOC variability. (1-43/49OC failed to be significantly associated to any PCOS trait. Conclusions Circulating ucOC concentration is related to key endocrine PCOS characteristics in a weight-dependent manner. Within the bone-pancreas loop, high ucOC may favor insulin release in lean hyperandrogenic women to compensate for

  7. The Anabolic Effect of PTH on Bone is Attenuated by Simultaneous Glucocorticoid Treatment

    DEFF Research Database (Denmark)

    Oxlund, Hans; Ørtoft, Gitte; Thomsen, Jesper Skovhus;

    2006-01-01

    a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group....... The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical...

  8. S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

    Science.gov (United States)

    Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

    1993-01-01

    The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S

  9. Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate: A Histomorphometric Study in Humans

    Directory of Open Access Journals (Sweden)

    Paulo José Pasquali

    2015-01-01

    Full Text Available Purpose. To investigate the regenerative results obtained with the association of bone marrow aspirate concentrate using the Bone Marrow Aspirate Concentrate (BMAC method to a xenogeneic bone graft (Bio-Oss in sinus floor elevation. Materials and Methods. Using a randomized controlled study design in eight consecutive patients (age of 55.4 ± 9.2 years, 16 sinus floor lift procedures were performed with Bio-Oss alone (control group, CG, n=8 or combined with bone marrow aspirate concentrate obtained via the BMAC method (test group, TG, n=8. Six months after the grafting procedures, bone biopsies were harvested during implant placement and were analyzed by histomorphometry. Results. Histomorphometric analysis revealed a significantly higher amount (p0.05 of nonmineralized tissue (38.53 ± 13.08% and 49.90 ± 7.64%, resp.. Conclusion. The use of bone marrow concentrate obtained by BMAC method increased bone formation in sinus lift procedures.

  10. Maxillary Sinus Augmentation Combining Bio-Oss with the Bone Marrow Aspirate Concentrate: A Histomorphometric Study in Humans

    Science.gov (United States)

    Pasquali, Paulo José; Teixeira, Marcelo Lucchesi; de Oliveira, Thiago Altro; de Macedo, Luis Guilherme Scavone; Aloise, Antonio Carlos; Pelegrine, André Antonio

    2015-01-01

    Purpose. To investigate the regenerative results obtained with the association of bone marrow aspirate concentrate using the Bone Marrow Aspirate Concentrate (BMAC) method to a xenogeneic bone graft (Bio-Oss) in sinus floor elevation. Materials and Methods. Using a randomized controlled study design in eight consecutive patients (age of 55.4 ± 9.2 years), 16 sinus floor lift procedures were performed with Bio-Oss alone (control group, CG, n = 8) or combined with bone marrow aspirate concentrate obtained via the BMAC method (test group, TG, n = 8). Six months after the grafting procedures, bone biopsies were harvested during implant placement and were analyzed by histomorphometry. Results. Histomorphometric analysis revealed a significantly higher amount (p 0.05) of nonmineralized tissue (38.53 ± 13.08% and 49.90 ± 7.64%, resp.). Conclusion. The use of bone marrow concentrate obtained by BMAC method increased bone formation in sinus lift procedures. PMID:26543482

  11. Relationships among maxillofacial morphologies, bone properties, and bone metabolic markers in patients with jaw deformities.

    Science.gov (United States)

    Saito, D; Mikami, T; Oda, Y; Hasebe, D; Nishiyama, H; Saito, I; Kobayashi, T

    2016-08-01

    The aim of this study was to determine the relationships among bone properties, bone metabolic markers, and types of jaw deformity. The subjects were 55 female patients with jaw deformities. Skeletal morphology was examined using lateral cephalograms, and the patients were divided into three groups according to the type of anteroposterior skeletal pattern. Serum osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b, as well as deoxypyridinoline in urine, were measured as bone metabolic markers. Quantitative ultrasound (QUS) measurements were used to assess bone properties at the calcaneal bone. The bone volume and bone density of the condylar process were measured in 43 patients by computed tomography. There were no significant differences in bone metabolic markers and QUS parameters between the groups, although bone formation and resorption markers tended to be higher in patients with a protrusive mandible. On the other hand, patients with mandibular retrusion had a higher tendency to have small and dense condylar processes. In conclusion, the results suggest that growth depression or a degenerative change in the mandibular condyle is involved in the pathogenesis of mandibular retrusion, although risk factors for progressive condylar resorption were not determined.

  12. Bone biomarkers of ovariectomised rats after leptin therapy.

    Science.gov (United States)

    Abdel-Sater, Khaled A; Mansour, Hamdy

    2013-01-01

    Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states, osteoporosis included, arise when this delicate balance is disrupted, such as in menopause. The aim of the present work was to study the effect of leptin supplementation on bone metabolism in ovariectomized adult female rats by measuring indices of bone biomarkers. Forty adult female albino rats were chosen as an animal model for this study and divided into the four equal groups (n=10/group): Group I (control SHAM-operated group) received a single dose of buffer solution i.p. daily for eight weeks. Group II (ovariectomy group) received a single dose of buffer solution i.p. daily for eight weeks. Group III (alendronate group): Ovariectomized rats that received alendronate 0.1 mg/kg body weight i.p. daily for eight weeks. Group IV (leptin group): Ovariectomized rats that received leptin (10 µg/kg body weight) i.p. daily for eight weeks. The obtained serum is required for determination of: Serum osteocalcin, alkaline phosphatase, calcium and phosphorous levels. The obtained data revealed that treatment with alendronate or leptin caused a significant decrease of serum osteocalcin, specific bone alkaline phosphatase and urinary deoxypyridinoline levels compared to ovariectomy group, and there was no significant difference between both drugs. Leptin prevents ovariectomy induced increases in bone turnover in rats. Leptin therapy has a significant effect in treatment of ovariectomy induced osteoporosis in rats (Tab. 1, Ref. 32).

  13. Bone Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

  14. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  15. CXC receptor knockout mice: characterization of skeletal features and membranous bone healing in the adult mouse.

    Science.gov (United States)

    Bischoff, David S; Sakamoto, Taylor; Ishida, Kenji; Makhijani, Nalini S; Gruber, Helen E; Yamaguchi, Dean T

    2011-02-01

    The potential role of CXC chemokines bearing the glu-leu-arg (ELR) motif in bone repair was studied using a cranial defect (CD) model in mice lacking the CXC receptor (mCXCR(-/-) knockout mice), which is homologous to knockout of the human CXC receptor 2 (CXCR2) gene. During the inflammatory stage of bone repair, ELR CXC chemokines are released by inflammatory cells and serve as chemotactic and angiogenic factors. mCXCR(-/-) mice were smaller in weight and length from base of tail to nose tip, compared to WT littermates. DEXA analysis indicated that bone mineral density (BMD), bone mineral content (BMC), total area (TA), bone area (BA), and total tissue mass (TTM) were decreased in the mCXCR(-/-) mice at 6, 12, and 18 weeks of age. Trabecular bone characteristics in mCXCR(-/-) (% bone, connectivity, number, and thickness) were reduced, and trabecular spacing was increased as evidenced by μCT. There was no difference in bone formation or resorption indices measured by bone histomorphometry. Trabecular BMD was not altered. Cortical bone volume, BMD, and thickness were reduced; whereas, bone marrow volume was increased in mCXCR(-/-). Decreased polar moment of inertia (J) in the tibias/femurs suggested that the mCXCR(-/-) long bones are weaker. This was confirmed by three-point bending testing of the femurs. CDs created in 6-week-old male mCXCR(-/-) and WT littermates were not completely healed at 12 weeks; WT animals, however, had significantly more bone in-growth than mCXCR(-/-). New bone sites were identified using polarized light and assessed for numbers of osteocyte (OCy) lacunae and blood vessels (BlV) around the original CD. In new bone, the number of BlV in WT was >2× that seen in mCXCR(-/-). Bone histomorphometry parameters in the cranial defect did not show any difference in bone formation or resorption markers. In summary, studies showed that mCXCR(-/-) mice have (1) reduced weight and size; (2) decreased BMD and BMC; (3) decreased amounts of trabecular

  16. Mechanism of mineral formation in bone.

    Science.gov (United States)

    Anderson, H C

    1989-03-01

    The mechanism of mineral formation in bone is seen best where active new bone formation is occurring, e.g., in newly forming subperiosteal bone of the embryo, in the growing bone of young animals, and in healing rickets where the calcification process in osteoid is reactivated. A large body of ultrastructural evidence, using conventional and anhydrous methods for tissue preparation, has shown convincingly that extracellular matrix vesicles are present at or near the mineralization front in all of the above, and that these vesicles are the initial site of apatite mineral deposition. Thus bone resembles growth plate cartilage, predentin, and turkey tendon in having calcification initiated by matrix vesicles. Once the calcification cascade is begun, matrix vesicles are no longer needed to support mineralization and are consumed by the advancing mineralization front in which performed crystals serve as nuclei for the formation of new crystals. The rate of crystal proliferation is promoted by the availability of Ca2+, PO4(3-), and the presence of collagen, and retarded by naturally occurring inhibitors of mineralization such as proteoglycans and several noncollagenous calcium-binding proteins of bone including bone-Gla protein (osteocalcin), phosphoproteins, osteonectin, and alpha-2HS-glycoproteins. New electron microscopic immunocytochemical findings in our laboratory suggest that the origin of alkaline phosphatase-positive bone matrix vesicles is polarized to the mineral-facing side of osteoblasts and may be concentrated near the intercellular junctions of human embryonic osteoblasts.

  17. Bone mineral density and markers of bone turnover in patients with renal transplantation and regular hemodialysis

    Directory of Open Access Journals (Sweden)

    Samir M. Ibrahim,. Khalid H Abdel-Mageed, Magdi M El-Sharkawy

    2002-09-01

    Full Text Available Background: Decreased bone mineral density (BMD is a known complication for the uremic state antedating dialysis / renal transplantation (RTx. The issue of stabilized versus continued decrease of BMD especially on long-term basis, continues to be unresolved. Patients and Methods: !"#"hemodialysis (HD-#" $% " &'( &'(-group had been evaluated for metabolic bone changes by calcium homeostasis parameters (serum calcium, phosphorus, alkaline phosphatase "ALP" and vitamin D "calcitriol", markers of bone formation (bone alkaline phosphatase "BAP", osteocalcin "OC", N-terminal propeptide of collagen type I "PINP", bone resorption markers (pyridoline "PYL" and deoxypyridoline "DPYL", and intact parathyroid hormone (iPTH. Also, BMD had been assessed by dual energy x-ray absorptiometry (DEXA twice, at inclusion time and * ! "" Results: comparing both groups regarding calcium homeostasis, markers of bone turnover and iPTH showed non significant difference. However, there was a significant drop of BMD (as evidenced by T-score at follow up in the HD group, compared to stabilization of T-score for the RTx-group. Furthermore, annual T-score change was significantly more in HD-group, compared to RTx-group. Results also showed that, the best marker correlating with T-score annual changes and iPTH to be PINP. Irrespective of normal calcium homeostasis parameters, low BMD is a prevalent disorder among patients on regular HD and renal transplants.Conclusion: Follow up for * ! " %+ ,- ." % """"!to continued bone loss in patients on regular HD. This could raise recommendation for calcium and calcitriol supplementation, especially in the predialysis period, early post transplantation period, and continued guided replacement for those on maintenance HD. Serum PINP showed best correlations with BMD changes and iPTH and could be considered a reliable marker reflecting bone formation in those patients. Keywords: hemodialysis, renal transplantation, markers of bone

  18. Performance, intestinal histomorphometry, and blood parameters of post-weaning piglets receiving different levels of soy protein concentrate in the diet

    Directory of Open Access Journals (Sweden)

    Moisés Queiroz Resende

    2016-06-01

    Full Text Available ABSTRACT Seventy-two barrows were used to evaluate the effects of the use of soy protein concentrate (SPC in diets of post-weaning piglets on their performance, intestinal histomorphometry, and blood parameters. Piglets were weaned at 21 days of age and distributed in a randomized-block experimental design with four treatments (0, 3, 6, and 9% SPC, six replications, and three piglets per replication. Diets were formulated to meet the requirement of the piglets according to phases of 21 to 32, 33 to 42, and 43 to 66 days of age. Both feed and water were provided ad libitum during the entire experiment. The feed of the phase of 43 to 66 days was based on corn and soybean meal. In the period between 21 and 32 days of age, the use of SPC in the diet did not impact the daily weight gain (DWG or the daily feed intake (DFI of the piglets, whereas there was a linear effect on feed conversion (FC, which decreased as the levels of SPC in the feed were increased. In the period between 33 and 42 days of age, a linear effect was observed on FC, which increased as the level of SPC in the feed was increased. In this period, no effects of SPC were observed on DWG or DFI. Inclusion of SPC in the diets does not influence performance, intestinal histomorphometry, or blood parameters of piglets in the period between 21 and 66 days of age.

  19. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

  20. Quantitative assessment of bone defect healing by multidetector CT in a pig model

    Energy Technology Data Exchange (ETDEWEB)

    Riegger, Carolin; Kroepil, Patric; Lanzman, Rotem S.; Miese, Falk R.; Antoch, Gerald; Scherer, Axel [University Duesseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Jungbluth, Pascal; Hakimi, Mohssen; Wild, Michael [University Duesseldorf, Medical Faculty, Department of Traumatology and Hand Surgery, Duesseldorf (Germany); Hakimi, Ahmad R. [Universtity Duesseldorf, Medical Faculty, Department of Oral Surgery, Duesseldorf (Germany)

    2012-05-15

    To evaluate multidetector CT volumetry in the assessment of bone defect healing in comparison to histopathological findings in an animal model. In 16 mini-pigs, a circumscribed tibial bone defect was created. Multidetector CT (MDCT) of the tibia was performed on a 64-row scanner 42 days after the operation. The extent of bone healing was estimated quantitatively by MDCT volumetry using a commercially available software programme (syngo Volume, Siemens, Germany).The volume of the entire defect (including all pixels from -100 to 3,000 HU), the nonconsolidated areas (-100 to 500 HU), and areas of osseous consolidation (500 to 3,000 HU) were assessed and the extent of consolidation was calculated. Histomorphometry served as the reference standard. The extent of osseous consolidation in MDCT volumetry ranged from 19 to 92% (mean 65.4 {+-} 18.5%). There was a significant correlation between histologically visible newly formed bone and the extent of osseous consolidation on MDCT volumetry (r = 0.82, P < 0.0001). A significant negative correlation was detected between osseous consolidation on MDCT and histological areas of persisting defect (r = -0.9, P < 0.0001). MDCT volumetry is a promising tool for noninvasive monitoring of bone healing, showing excellent correlation with histomorphometry. (orig.)

  1. A New Piezoelectric Actuator Induces Bone Formation In Vivo: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Joana Reis

    2012-01-01

    Full Text Available This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth.

  2. Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

    Energy Technology Data Exchange (ETDEWEB)

    Schulz, W.; Schmidt, M.

    1986-12-01

    Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

  3. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Johansen, Lars Dan; Jensen, Anders Asbjørn;

    2009-01-01

    . Analogously to the closely related calcium-sensing receptor, GPRC6A has been proposed to function as a metabolic sensor of Ca2+ and amino acids in bone and other tissues. In the present study, we have generated the first GPRC6A knockout mice and studied their phenotype with particular focus on bone...... homeostasis. The generated GPRC6A knockout mice are viable and fertile, develop normally and exhibit no significant differences in body weight compared to wild type littermates. Assessment of bone mineral density, histomorphometry and bone metabolism demonstrated no significant differences between 13-week......-old knockout and wild type mice. In conclusion, our data do not support a role for GPRC6A in normal bone physiology....

  4. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model

    Directory of Open Access Journals (Sweden)

    Zil Hayatullina

    2012-01-01

    Full Text Available Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx, and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO. Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  5. Virgin coconut oil supplementation prevents bone loss in osteoporosis rat model.

    Science.gov (United States)

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.

  6. Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children

    DEFF Research Database (Denmark)

    Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni

    2016-01-01

    We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely...... associated with bone size in girls. INTRODUCTION: Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin.......017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/μg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). CONCLUSIONS: This large longitudinal study suggests that in 8- to 11-year-old children, IGF...

  7. Combined intervention of dietary soybean proteins and swim training: effects on bone metabolism in ovariectomized rats.

    Science.gov (United States)

    Figard, Hélène; Mougin, Fabienne; Gaume, Vincent; Berthelot, Alain

    2006-01-01

    Soybean proteins, a rich source of isoflavones, taken immediately after an ovariectomy prevent bone loss in rats. Exercise-induced stimuli are essential for bone growth. Few studies exist about the combined effects of swim training and soybean protein supplementation on bone metabolism. So, the purpose of this study was to investigate, in 48 female Sprague-Dawley rats (12 weeks old) the effects of an 8-week swim-training regimen (1 h/day, 5 days/week) and dietary soybean proteins (200 g/kg diet) on bone metabolism. Rats were randomly assigned to four groups: (1) ovariectomized fed with a semisynthetic control diet; (2) ovariectomized fed with a soybean protein-enriched semisynthetic diet; (3) ovariectomized trained to exercise and fed with control diet; (4) ovariectomized trained to exercise and fed with a soybean protein diet. Following the treatment period, body weight gain was identical in the four groups. Soybean protein supplementation increased bone calcium content, and reduced plasma osteocalcin values, without significant modification of calcium balance and net calcium absorption. Swim training enhanced plasma and bone calcium content and calcium balance and net calcium absorption. It did not modify either plasma osteocalcin values or urinary deoxypyridinoline excretion. Both exercise and soybean protein intake increased plasma on bone calcium without modifying net calcium absorption or bone markers. In conclusion, we demonstrated, in ovariectomized rats, that swimming exercise and dietary supplementation with soy proteins do not have synergistic effects on calcium metabolism and bone markers.

  8. New laboratory tools in the assessment of bone quality.

    Science.gov (United States)

    Chappard, D; Baslé, M F; Legrand, E; Audran, M

    2011-08-01

    Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent. The bone matrix organization can be described at five different levels of anatomical organization: nature (organic and mineral), texture (woven or lamellar), structure (osteons in the cortices and arch-like packets in trabecular bone), microarchitecture, and macroarchitecture. Any change in one of these levels can alter bone quality. An altered bone remodeling can affect bone quality by influencing one or more of these factors. We have reviewed here the main methods that can be used in the laboratory to explore bone quality on bone samples. Bone remodeling can be evaluated by histomorphometry; microarchitecture is explored in 2D on histological sections and in 3D by microCT or synchrotron. Microradiography and scanning electron microscopy in the backscattered electron mode can measure the mineral distribution; Raman and Fourier-transformed infra-red spectroscopy and imaging can simultaneously explore the organic and mineral phase of the matrix on multispectral images; scanning acoustic microscopy and nanoindentation provide biomechanical information on individual trabeculae. Finally, some histological methods (polarization, surface staining, fluorescence, osteocyte staining) may also be of interest in the understanding of quality as a component of bone fragility. A growing number of laboratory techniques are now available. Some of them have been described many years ago and can find a new youth; others having benefited from improvements in physical and computer techniques are now available.

  9. The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype.

    Science.gov (United States)

    Nimptsch, Katharina; Nieters, Alexandra; Hailer, Susanne; Wolfram, Günther; Linseisen, Jakob

    2009-06-01

    Vitamin K acts as a cofactor during the gamma-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18-81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83.4/37.6 microg/d in men and 79.6/29.8 microg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene.

  10. LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

    Institute of Scientific and Technical Information of China (English)

    Changjun Li; Bart O Williams; Xu Cao; Mei Wan

    2014-01-01

    Lipoprotein receptor-related protein 6 (LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells (MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin1 MSCs by crossing nestin-Cre mice with LRP6flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin1 cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT (mCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix1 osteoprogenitors and osteocalcin1 osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

  11. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.

    Science.gov (United States)

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn; O'Connor, J Patrick

    2015-07-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

  12. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats.

    Science.gov (United States)

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei

    2012-06-01

    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  13. Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects

    Directory of Open Access Journals (Sweden)

    D.C.L. Carvalho

    2006-10-01

    Full Text Available Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 ± 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11 and control (N = 10 groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.

  14. Interactions between muscle tissues and bone metabolism.

    Science.gov (United States)

    Kawao, Naoyuki; Kaji, Hiroshi

    2015-05-01

    Sarcopenia and osteoporosis have recently been noted for their relationship with locomotive syndrome and increased number of older people. Sarcopenia is defined by decreased muscle mass and impaired muscle function, which may be associated with frailty. Several clinical data have indicated that increased muscle mass is related to increased bone mass and reduced fracture risk. Genetic, endocrine and mechanical factors as well as inflammatory and nutritional states concurrently affect muscle tissues and bone metabolism. Several genes, including myostatin and α-actinin 3, have been shown in a genome-wide association study (GWAS) to be associated with both sarcopenia and osteoporosis. Vitamin D, growth hormone and testosterone as well as pathological disorders, such as an excess in glucocorticoid and diabetes, affect both muscle and bone. Basic and clinical research of bone metabolism and muscle biology suggests that bone interacts with skeletal muscle via signaling from local and humoral factors in addition to their musculoskeletal function. However, the physiological and pathological mechanisms related to muscle and bone interactions remain unclear. We found that Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage. We also reported that osteoglycin and FAM5C might be muscle-derived humoral osteogenic factors. Other factors, including myostatin, osteonectin, insulin-like growth factor I, irisin and osteocalcin, may be associated with the interactions between muscle tissues and bone metabolism. © 2014 Wiley Periodicals, Inc.

  15. Locally delivered salicylic acid from a poly(anhydride-ester): impact on diabetic bone regeneration.

    Science.gov (United States)

    Wada, Keisuke; Yu, Weiling; Elazizi, Mohamad; Barakat, Sandrine; Ouimet, Michelle A; Rosario-Meléndez, Roselin; Fiorellini, Joseph P; Graves, Dana T; Uhrich, Kathryn E

    2013-10-10

    Diabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague-Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4weeks but not at 12weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals.

  16. Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats.

    Science.gov (United States)

    Wronski, T J; Dann, L M; Scott, K S; Crooke, L R

    1989-08-01

    This study was designed to test the hypothesis that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during estrogen deficiency. Sham-operated control and ovariectomized (OVX) rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and NE-58095 [2-(3-pyridinyl)2-hydroxyethylidene-1,1-bisphosphonate disodium] for 35 or 70 days after surgery. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Vehicle-treated OVX rats were characterized by decreased cancellous bone volume and 3- to 4-fold increases in osteoblast surface, osteoclast surface, bone formation rate, and bone resorption rate. Treatment of OVX rats with estrogen and NE-58095 provided complete protection against bone loss and significantly depressed all of the above indices of bone turnover. OVX rats treated with EHDP exhibited at least partial protection against bone loss and decreased bone turnover. EHDP induced a mild mineralization defect, as indicated by a prolonged mineralization lag time at the tibial endocortical surface. The new diphosphonate compound NE-58095 did not impair bone mineralization. Our results indicate that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during the early stages of estrogen deficiency. If confirmed by clinical trials in humans, diphosphonate compounds may prove to be an alternative to estrogen for the prevention of postmenopausal bone loss.

  17. Bone repair: Effects of physical exercise and LPS systemic exposition.

    Science.gov (United States)

    Nogueira, Jonatas E; Branco, Luiz G S; Issa, João Paulo M

    2016-08-01

    Bone repair can be facilitated by grafting, biochemical and physical stimulation. Conversely, it may be delayed lipopolysaccharide (LPS). Physical exercise exerts beneficial effects on the bone, but its effect on bone repair is not known. We investigated the effect of exercise on the LPS action on bone healing through bone densitometry, quantitative histological analysis for bone formation rate and immunohistochemical markers in sedentary and exercised animals. Rats ran on the treadmill for four weeks. After training the rats were submitted to a surgical procedure (bone defect in the right tibia) and 24h after the surgery LPS was administered at a dose of 100μg/kg i.p., whereas the control rats received a saline injection (1ml/kg, i.p.). Right tibias were obtained for analysis after 10days during which rats were not submitted to physical training. Physical exercise had a positive effect on bone repair, increasing bone mineral density, bone mineral content, bone formation rate, type I collagen and osteocalcin expression. These parameters were not affected by systemic administration of LPS. Our data indicate that physical exercise has an important osteogenic effect, which is maintained during acute systemic inflammation induced by exposure to a single dose of LPS.

  18. Bone Formation in Maxillary Sinus Lift Using Autogenous Bone Graft at 2 and 6 Months

    Science.gov (United States)

    Netto, Henrique Duque; Miranda Chaves, Maria das Graças Alfonso; Aatrstrup, Beatriz; Guerra, Renata; Olate, Sergio

    2016-01-01

    SUMMARY The aim of this study is to compare the bone formation in maxillary sinus lift with an autogenous bone graft in histological evaluation at 2 or 6 months. A comparative study was designed where 10 patients with missing teeth bilaterally in the posterior zone of the maxilla were selected. Patients received a particulate autogenous bone graft under the same surgical conditions, selecting a site to collect a biopsy and histological study at two months and another at six months postoperatively. Histomorphometry was performed and were used Kolmogorov-Smirnov test, student’s t-test and Spearman’s correlation coefficient, considering a value of p<0.05. Differences were observed in inflammatory infiltrate and vascularization characteristics; however, the group analyzed at two months presented 38.12% ± 6.64 % of mineralized tissue, whereas the group studied at 6 months presented an average of 38.45 ± 9.27 %. There were no statistical differences between the groups. It is concluded that the bone formation may be similar in intrasinus particulate autogenous bone grafts in evaluations at two or six months; under these conditions, early installation of implants is viable. PMID:27867255

  19. Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome

    Directory of Open Access Journals (Sweden)

    Stefano Stagi

    2016-01-01

    Full Text Available Objective. Klinefelter syndrome (KS has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7±3.8 years KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH, 25-hydroxyvitamin D (25(OHD, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS and the bone transmission time (BTT. Results. KS children and adolescents showed significantly reduced AD-SoS (p<0.005 and BTT (p<0.0005 z-scores compared to the controls. However, KS patients presented significantly higher PTH (p<0.0001 and significantly lower 25(OHD (p<0.0001, osteocalcin (p<0.05, and bone alkaline phosphatase levels (p<0.005. Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages.

  20. Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome

    Science.gov (United States)

    Stagi, Stefano; Di Tommaso, Mariarosaria; Manoni, Cristina; Scalini, Perla; Chiarelli, Francesco; Verrotti, Alberto; Lapi, Elisabetta; Giglio, Sabrina; Dosa, Laura; de Martino, Maurizio

    2016-01-01

    Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7 ± 3.8 years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD-SoS (p < 0.005) and BTT (p < 0.0005) z-scores compared to the controls. However, KS patients presented significantly higher PTH (p < 0.0001) and significantly lower 25(OH)D (p < 0.0001), osteocalcin (p < 0.05), and bone alkaline phosphatase levels (p < 0.005). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages. PMID:27413371

  1. Pregnancy and Lactation-Associated Osteoporosis: Bone Histomorphometric Analysis and Response to Treatment with Zoledronic Acid.

    Science.gov (United States)

    Grizzo, Felipe Merchan Ferraz; da Silva Martins, Janaina; Pinheiro, Marcelo M; Jorgetti, Vanda; Carvalho, Maria Dalva Barros; Pelloso, Sandra Marisa

    2015-10-01

    Pregnancy and lactation-associated osteoporosis (PAO) is a rare condition with little known pathophysiology. Most cases are diagnosed in the third trimester of pregnancy or in the first weeks postpartum, particularly in first pregnancies. Vertebral fractures are most commonly observed and characterised by prolonged severe pain, functional limitations and a loss of height. Measurements of bone mineral density and biochemical markers of bone remodelling are the clinical methods most commonly used for the management of these patients. However, a bone biopsy with histomorphometric analysis has been considered to be the gold-standard. Few studies have evaluated the histomorphometry in patients with this clinical condition and none of them performed the procedure at the beginning of the clinical assessment. In this study, we report a case of PAO in a 31-year-old postpartum patient who had undergone a twin pregnancy. We describe the clinical, laboratory tests and imaging features. Bone histomorphometry showed a high resorption rate and excellent evolution after 1 year of treatment with intravenous zoledronic acid. Our data suggest that osteoclastogenesis plays a central role in the pathophysiological processes of this disease.

  2. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen

    2000-01-01

    factor (TNF) alpha, TNFbeta, and transforming growth factor (TGF) beta in marrow plasma aspirated from the biopsy area. MARKERS OF BONE RESORPTION: The N-terminal telopeptide of collagen I (Ntx) in urine showed a strong positive correlation with the dynamic histomorphometric indices of bone resorption (r...... with the histomorphometric findings. MARKERS OF BONE FORMATION: Serum C-terminal propeptide of procollagen I (PICP) and serum bone-specific alkaline phosphatase (bAP) showed significant correlations with the dynamic parameters of bone formation (r=0.57-0.58), whereas serum osteocalcin and serum total AP did not. CYTOKINES...... that measurements of the biochemical markers of bone metabolism may be useful in monitoring myeloma bone disease, and might thus be of use for dose titration of bisphosphonate therapy....

  3. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  4. Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal.

    Science.gov (United States)

    Wergedal, Jon E; Veskovic, Katarina; Hellan, Minea; Nyght, Christine; Balemans, Wendy; Libanati, Cesar; Vanhoenacker, Filip M; Tan, Johan; Baylink, David J; Van Hul, Wim

    2003-12-01

    Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 +/- 33% and 497 +/- 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.

  5. Bone mass and bone metabolic indices in male master rowers.

    Science.gov (United States)

    Śliwicka, Ewa; Nowak, Alicja; Zep, Wojciech; Leszczyński, Piotr; Pilaczyńska-Szcześniak, Łucja

    2015-09-01

    The purpose of this study was to assess bone mass and bone metabolic indices in master athletes who regularly perform rowing exercises. The study was performed in 29 men: 14 master rowers and 15 non-athletic, body mass index-matched controls. Dual-energy X-ray absorptiometry measurements of the areal bone mineral density (aBMD) were performed for the total body, regional areas (arms, total forearms, trunk, thoracic spine, pelvis, and legs), lumbar spine (L1-L4), left hip (total hip and femoral neck), and forearm (33 % radius of the dominant and nondominant forearm). Serum concentrations of osteocalcin, collagen type I cross-linked C-telopeptide, visfatin, resistin, insulin, and glucose were determined. Comparative analyses showed significantly lower levels of body fat and higher lean body mass values in the rowers compared to the control group. The rowers also had significantly higher values of total and regional (left arm, trunk, thoracic spine, pelvis, and leg) BMD, as well as higher BMD values for the lumbar spine and the left hip. There were significant differences between the groups with respect to insulin, glucose, and the index of homeostasis model assessment insulin resistance. In conclusion, the systematic training of master rowers has beneficial effects on total and regional BMD and may be recommended for preventing osteoporosis.

  6. Effect of collagen sponge and fibrin glue on bone repair

    Directory of Open Access Journals (Sweden)

    Thiago de Santana SANTOS

    2015-12-01

    Full Text Available ABSTRACT The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. Material and Methods Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p≤0.05. Results Three-dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. Conclusion Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous.

  7. Effects of salvianolate on bone metabolism in glucocorticoid-treated lupus-prone B6.MRL-Faslpr/J mice

    Science.gov (United States)

    Liu, Yanzhi; Cui, Yang; Zhang, Xiao; Gao, Xiang; Su, Yanjie; Xu, Bilian; Wu, Tie; Chen, Wenshuang; Cui, Liao

    2016-01-01

    Aim To investigate the bone-protective effects of salvianolate (Sal), a total polyphenol from Radix Salviae miltiorrhizae, on bone tissue in the spontaneous lupus-prone mouse model, B6.MRL-Faslpr/J, undergoing glucocorticoid (GC) treatment. Methods Fifteen-week-old female B6.MRL-Faslpr/J mice were administered either a daily dose of saline (lupus group), prednisone 6 mg/kg (GC group), Sal 60 mg/kg (Sal group); or GC plus Sal (GC + Sal group) for a duration of 12 weeks. Age-matched female C57BL/6J wild-type (WT) mice were used for control. Micro-computed tomography assessments, bone histomorphometry analysis, bone biomechanical test, immunohistochemistry and immunoblotting analysis for bone markers, and renal histology analysis were performed to support our research endeavor. Results Lupus mice developed a marked bone loss and deterioration of mechanical properties of bone due to an increase in bone resorption rather than suppression of bone formation. GC treatment strongly inhibited bone formation in lupus mice. Sal treatment significantly attenuated osteogenic inhibition, and also suppressed hyperactive bone resorption, which recovered the bone mass and mechanical properties of bone in both the untreated and GC-treated lupus mice. Conclusion The data support further preclinical investigation of Sal as a potential therapeutic strategy for the treatment of systemic lupus erythematosus-related bone loss. PMID:27563234

  8. Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Fu, Song-wen; Zeng, Gao-feng; Zong, Shao-hui; Zhang, Zhi-yong; Zou, Bin; Fang, Ye; Lu, Li; Xiao, De-qiang

    2014-06-01

    Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments have been designed to investigate the preventive effects of phytoestrogens for osteoporosis; however, it is easy for a single dissenting result from animal experiments to mislead clinical investigations. Herein, we use meta-analysis to assess the evidence for a protective effect of phytoestrogens on ovariectomized rat models of osteopenia. With respect to osteoporosis, PubMed and Web of Science were searched from January 2000 to March 2013 for relevant studies of phytoestrogens in ovariectomized rats. Two reviewers independently selected and assessed the studies. Data were aggregated using a random effects model. Meta-analysis revealed that the phytoestrogen treatment group demonstrated a significantly higher femur bone mineral density and trabecular bone and lower bone turnover markers (serum alkaline phosphatase and serum osteocalcin) compared with the control ovariectomized group, thus showing a bone protective effect of phytoestrogens in ovariectomized rats. Subsequent sensitivity analyses indicated that the effect of phytoestrogens on serum alkaline phosphatase and serum osteocalcin are not robust. Despite the high heterogeneity in the systematic review of animal experiments, the present results indicated that phytoestrogens may offer the most potential for the prevention of bone loss by reducing the expected loss of trabecular bone and bone mineral density. Their effects are likely due to inhibition of bone resorption, but their benefits on bone formation are still unclear. Further studies are needed to assess the effect of phytoestrogens on bone formation and the efficacy and safety of individual phytoestrogens.

  9. 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......Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear....... We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose...

  10. Surface-modified functionalized polycaprolactone scaffolds for bone repair

    DEFF Research Database (Denmark)

    Jensen, Jonas; Rölfing, Jan Hendrik Duedal; Svend Le, Dang Quang

    2014-01-01

    into two groups with 8 and 12 weeks follow-up, respectively. A total of six nonpenetrating holes were drilled in the calvaria of each animal. The size of the cylindrical defects was h 10 mm and Ø 10 mm. The defects were distributed randomly using following groups: (a) NSP-PCL scaffold, (b) FDM-PCL scaffold......, (c) autograft, (d) empty defect, (a1) NSP-PCL scaffold + autologous mononuclear cells, and (a2) NSP-PCL scaffold + bone morphogenetic protein 2. Bone volume to total volume was analyzed using microcomputed tomography (µCT) and histomorphometry. The µCT and histological data showed significantly less...... were heavily infiltrated with foreign body giant cells suggesting an inflammatory response and perhaps active resorption of the scaffold material. The unmodified FDM-PCL scaffold showed good osteoconductivity and osseointegration after both 8 and 12 weeks....

  11. Digital image processing of bone - Problems and potentials

    Science.gov (United States)

    Morey, E. R.; Wronski, T. J.

    1980-01-01

    The development of a digital image processing system for bone histomorphometry and fluorescent marker monitoring is discussed. The system in question is capable of making measurements of UV or light microscope features on a video screen with either video or computer-generated images, and comprises a microscope, low-light-level video camera, video digitizer and display terminal, color monitor, and PDP 11/34 computer. Capabilities demonstrated in the analysis of an undecalcified rat tibia include the measurement of perimeter and total bone area, and the generation of microscope images, false color images, digitized images and contoured images for further analysis. Software development will be based on an existing software library, specifically the mini-VICAR system developed at JPL. It is noted that the potentials of the system in terms of speed and reliability far exceed any problems associated with hardware and software development.

  12. Effects of Sigma Anti-bonding Molecule Calcium Carbonate on bone turnover and calcium balance in ovariectomized rats.

    Science.gov (United States)

    Choi, So-Young; Park, Dongsun; Yang, Goeun; Lee, Sun Hee; Bae, Dae Kwon; Hwang, Seock-Yeon; Lee, Paul K; Kim, Yun-Bae; Kim, Ill-Hwa; Kang, Hyun-Gu

    2011-12-01

    This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

  13. Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys.

    Science.gov (United States)

    Kostenuik, Paul J; Smith, Susan Y; Samadfam, Rana; Jolette, Jacquelin; Zhou, Lei; Ominsky, Michael S

    2015-04-01

    Postmenopausal osteoporosis is a chronic disease wherein increased bone remodeling reduces bone mass and bone strength. Antiresorptive agents including bisphosphonates are commonly used to mitigate bone loss and fracture risk. Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer approach for reducing fracture risk in patients at increased risk for fracture. The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One day after OVX, cynos (7-10/group) were treated with vehicle (VEH, s.c.), ALN (50 μg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other animals received VEH or ALN for 6 months and then transitioned to 6 months of DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and transition from ALN to DMAb caused further reductions relative to continued ALN. DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb resulted in a lesser decline in Ca relative to DMAb or to VEH-DMAb transition. Bone histomorphometry indicated significantly reduced trabecular and cortical remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling, and transition from ALN to DMAb reduced these parameters relative to continued ALN. Bone mineral density increased in all active treatment groups relative to VEH controls. Destructive biomechanical testing revealed significantly greater vertebral strength in all three groups receiving DMAb, including those receiving DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly correlated in all groups at all tested skeletal sites, consistent with normal bone quality. These data indicate that cynos transitioned from ALN to DMAb exhibited reduced bone resorption and cortical porosity, and increased BMD and bone strength, without

  14. Young Coconut Juice Supplementation Results in Greater Bone Mass and Bone Formation Indices in Ovariectomized Rats: A Preliminary Study.

    Science.gov (United States)

    Morii, Yuko; Matsushita, Hiroshi; Minami, Akira; Kanazawa, Hiroaki; Suzuki, Takashi; Subhadhirasakul, Sanan; Watanabe, Kazushi; Wakatsuki, Akihiko

    2015-12-01

    Young coconut juice (Cocos nucifera Linn.) (YCJ) has traditionally been consumed to alleviate symptoms associated with menopause by women in Southeast Asia. The aim of the present study was to determine the effects of YCJ on bone metabolism in ovariectomized rats. Female 10-week-old Wistar rats were randomly assigned to the following 4 groups: Baseline, Sham, Ovx, and Ovx + YCJ (n = 10 rats per group). Rats in the Baseline group were sacrificed immediately, and those in the other groups were subjected to either sham operation (Sham) or bilateral ovariectomy (Ovx and Ovx + YCJ). The Ovx + YCJ rats were administered 5×-concentrated YCJ at a dose of 10 mL/kg body weight per day. Six weeks after surgery, the rats were sacrificed, and indices of bone mass and bone histomorphometry were measured. The bone mineral density of the left femur was significantly higher in the Ovx + YCJ group compared with the Ovx group. In addition, the Ovx + YCJ group showed significantly higher measurements for bone formation rate compared with the Ovx group. These findings suggest that YCJ supplementation has a positive effect on bone metabolism and thus represents a possible intervention to slow the bone loss observed following menopause.

  15. Effects of Vitamin E on Bone Biomechanical and Histomorphometric Parameters in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Rafaela G. Feresin

    2013-01-01

    Full Text Available The present study examined the dose-dependent effect of vitamin E in reversing bone loss in ovariectomized (Ovx rats. Sprague-Dawley rats were either Sham-operated (Sham or Ovx and fed control diet for 120 days to lose bone. Subsequently, rats were divided into 5 groups (n=12/group: Sham, Ovx-control, low dose (Ovx + 300 mg/kg diet; LD, medium dose (Ovx + 525 mg/kg diet; MD, and high dose (Ovx + 750 mg/kg diet; HD of vitamin E and sacrificed after 100 days. Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase compared to the Ovx-control group. Bone histomorphometry analysis indicated a decrease in bone resorption as well as increased bone formation and mineralization in the Ovx groups supplemented with MD and HD of vitamin E. Microcomputed tomography findings indicated no effects of vitamin E on trabecular bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced fourth lumbar vertebra quality as evidenced by improved ultimate and yield load and stress when compared to Ovx-control group. These findings demonstrate that vitamin E improves bone quality, attenuates bone resorption, and enhances the rate of bone formation while being unable to restore bone density and trabecular bone structure.

  16. Relationship between vitamin D, parathyroid hormone, and bone health.

    Science.gov (United States)

    Sai, A J; Walters, R W; Fang, X; Gallagher, J C

    2011-03-01

    There is a controversy regarding the definition of vitamin D insufficiency as it relates to bone health. The objective of the study was to examine the evidence for a threshold value of serum 25-hydroxyvitamin D (25OHD) that defines vitamin D insufficiency as it relates to bone health. This was a cross-sectional analysis of baseline data in 488 elderly Caucasian women, mean age 71 yr, combined with a literature review of 70 studies on the relationship of serum PTH to serum 25OHD. The study was conducted in independent-living women in the midwest United States. The relationship between serum 25OHD, serum PTH, and serum osteocalcin and 24-h urine N-telopeptides was evaluated. Serum PTH was inversely correlated with serum 25OHD (r = -0.256, P bone markers, serum osteocalcin and urine N-telopeptides, that increased only below a serum 25OHD of approximately 18 ng/ml (45 nmol/liter). Calcium absorption was not correlated with serum PTH and serum 25OHD, and no threshold was found. A literature review of 70 studies generally showed a threshold for serum PTH with increasing serum 25OHD, but there was no consistency in the threshold level of serum 25OHD that varied from 10 to 50 ng/ml (25-125 nmol/liter). Vitamin D insufficiency should be defined as serum 25OHD less than 20 ng/ml (50 nmol/liter) as it relates to bone.

  17. DIAGNOSTICS OF BONE METABOLISM DISORDERS IN ONCOLOGICAL DISEASES

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    O. I. Apolikhin

    2015-01-01

    Full Text Available Osteoporosis is one of the most significant bone complications of cancer. About 1.5 million cancer patients worldwide have bone metastases. Patients with myeloma, breast cancer, prostate, thyroid, bladder and lung have very high risk of development of bone lesions and related complications. Currently, osteodensitometry is the gold standard for the diagnosis of osteoporosis. In recent years we frequently use the innovative imaging techniques for bone metastases, such as CT, MRI, PET/CT. Unfortunately, the diagnostic value of these methods is that it is not always possible to identify abnormalities of bone metabolism in cancer, especially in the early stages. This review shows the world experience of usage of biochemical markers of bone resorption (calcium, hydroxyproline, NTX, CTX, PYD, DPD, TRAP-5b, bone sialoprotein - BSP and markers of bone synthesis (osteocalcin, CSF, ACF, Karlovy vary IFF, their advantages and disadvantages. The level of these markers is increased in most patients with osteoporosis and bone metastases, it is suggesting a potential role in early diagnosis of bone metastases.

  18. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Petrizzi, Lucio; Mariscoli, Massimo; Valbonetti, Luca; Varasano, Vincenzo; Langhoff, Jens D; von Rechenberg, Brigitte

    2007-01-01

    Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a p...

  19. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Petrizzi, Lucio; Mariscoli, Massimo; Valbonetti, Luca; Varasano, Vincenzo; Langhoff, Jens D; von Rechenberg, Brigitte

    2007-01-01

    BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a ...

  20. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Langhoff Jens D; Varasano Vincenzo; Valbonetti Luca; Mariscoli Massimo; Petrizzi Lucio; Von Rechenberg Brigitte

    2007-01-01

    Abstract Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxo...

  1. Is Lipid Profile Associated with Bone Mineral Density and Bone Formation in Subjects with Spinal Cord Injury?

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    Hadis Sabour

    2014-01-01

    Full Text Available Purpose. The association between serum lipids and bone mineral density (BMD has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI. We tried to assess the correlation between serum triglyceride (TG, total cholesterol (TC, high-density lipoprotein (HDL, and low-density lipoprotein (LDL and BMD in male subjects with SCI. Methods. Dual-energy X-ray absorptiometry (DXA was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX, and bone alkaline phosphatase (BALP. Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age. Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004, r=0.33. HDL was negatively correlated with osteocalcin (P: 0.017, r=-0.31 which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD. Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation.

  2. Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats

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    Tábata de Mello TERA

    2014-12-01

    Full Text Available Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an expanded polytetrafluoroethylene (e-PTFE membrane using immunohistochemistry in rats with induced estrogen deficiency. Material and Methods Eighty female rats were randomly divided into two groups: ovariectomized (OVX and with a simulation of the surgical procedure (SHAM. Each of these groups was again divided into groups with either placement of an autogenous bone graft alone (BG or an autogenous bone graft associated with an e-PTFE membrane (BGM. Animals were euthanized on days 0, 7, 21, 45, and 60. The specimens were subjected to immunohistochemistry for bone sialoprotein (BSP, osteonectin (ONC, and osteocalcin (OCC. Results All groups (OVX+BG, OVX+BMG, SHAM+BG, and SHAM+BMG showed greater bone formation, observed between 7 and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone graft showed direct bonding to the recipient bed in all specimens. The ONC and OCC showed more expressed in granulation tissue, in the membrane groups, independently of estrogen deficiency. Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency. However, the markers could be influenced by the presence of the e-PTFE membrane.

  3. Effects of taurine supplementation on bone mineral density in ovariectomized rats fed calcium deficient diet.

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    Choi, Mi-Ja

    2009-01-01

    Taurine supplementation has been shown to have a beneficial effect on femur bone mineral content in ovariectomized rats. It therefore seemed desirable to find out whether the beneficial effect of taurine on ovariectomized rats fed calcium deficient diet could also be reproduced. Forty female Sprague-Dawley rats were divided into two groups. One group was OVX and the other group received sham operation (SHAM), and received either control diet or a taurine supplemented diet for 6 weeks. All rats were fed on calcium deficient diet (AIN-93: 50% level of calcium) and deionized water. Bone mineral density (BMD) and bone mineral content (BMC) were measured in spine and femur. The serum and urine concentrations of calcium and phosphorus were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Urinary calcium and phosphorus excretion, osteocalcin in blood and cross link value were not significantly different among the groups. Within the OVX group, the taurine supplemented group had not higher femur bone mineral content than the control group. This study established the need for a study on the taurine effect on bone with different calcium levels.

  4. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats

    Institute of Scientific and Technical Information of China (English)

    Hua MAN; Lu-ping QIN; Wan-sheng CHEN; Qiao-yan ZHANG; Han-chen ZHENG; Yin WANG

    2006-01-01

    Aim: To investigate the protective effect of steroidal saponins from Anemarrhena asphodeloides (ATS) on ovariectomy (OVX)-induced bone loss. Methods: Sprague-Dawley rats were divided into sham and OVX groups. The OVX rats were treated with vehicle, nylestriol or steroidal saponins extract for 12 weeks. Serum calcium, phosphorus, estradiol (E2), osteocalcin concentration and serum alkaline phosphatase activity were measured. Bone density was assayed by dual-energy X-ray absorptiometry. The undecalcified longitudinal proximal tibial metaphysical (PTM) sections were cut and stained for histomorphometric analysis of the bone. Results: In OVX rats, alkaline phosphatase activities in serum were markedly increased and concentrations of osteocalcin were decreased by ATS treatment, which had no influence on the body weight. Meanwhile, atrophy of the uterus and descent of bone mineral density (BMD) was suppressed by treatment with ATS. In addition, ATS completely corrected the decreased the concentration of calcium and E2 in serum observed in OVX rats. Histological results showed ATS prevented decreases in trabecular thickness and increases in trabecular separation of proximal tibia metaphysis (PTM) in OVX rats. However, it did not alter osteoclast number in OVX rats. Moreover, ATS (300 mg/kg) had a remarkable effect on promoting bone formation action in OVX rats. Nylestriol treatment decreased the bone formation rate and mineral apposition rate. Conclusion: An adequate supply of steroidal saponins of Anemarrhena asphodeloides prevented OVX-induced bone loss in rats through the promotion of bone formation but not the inhibition of bone resorption.

  5. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Mondy, Kristin; Yarasheski, Kevin; Powderly, William G; Whyte, Michael; Claxton, Sherry; DeMarco, Debra; Hoffmann, Mary; Tebas, Pablo

    2003-02-15

    The underlying mechanisms of several bone disorders in human immunodeficiency virus (HIV)-infected persons and any relation to antiretroviral therapy have yet to be defined. A longitudinal study was conducted to estimate the prevalence of osteopenia or osteoporosis in HIV-infected persons; to assess bone mineralization, metabolism, and histomorphometry over time; and to evaluate predisposing factors. A total of 128 patients enrolled the study, and 93 were observed for 72 weeks. "Classic" risk factors (low body mass index, history of weight loss, steroid use, and smoking) for low bone mineral density (BMD) and duration of HIV infection were strongly associated with osteopenia. There was a weak association between low BMD and receipt of treatment with protease inhibitors; this association disappeared after controlling for the above factors. Markers of bone turnover tended to be elevated in the whole cohort but were not associated with low BMD. BMD increased slightly during follow-up. Traditional risk factors and advanced HIV infection play a more significant pathogenic role in the development of osteopenia and osteoporosis associated with HIV infection than do treatment-associated factors.

  6. Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism.

    Science.gov (United States)

    Zhou, Bo; Li, Huixia; Liu, Jiali; Xu, Lin; Zang, Weijin; Wu, Shufang; Sun, Hongzhi

    2013-06-15

    The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in cardiovascular disease (CVD) is not fully understood. In the present study, we investigated the effect of osteocalcin on autophagy and endoplasmic reticulum (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and in vascular cell models and clarified the intracellular events responsible for osteocalcin-mediated effects. The evidences showed that intermittent injections of osteocalcin in mice fed the high-fat diet were associated with a reduced body weight gain, decreased blood glucose and improved insulin sensitivity compared with mice fed the high-fat diet receiving vehicle. Simultaneously, the administration of osteocalcin not only attenuated autophagy and ER stress but also rescued impaired insulin signaling in vascular tissues of mice fed a high-fat diet. Consistent with these results in vivo, the addition of osteocalcin reversed autophagy and ER stress and restored defective insulin sensitivity in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the presence of tunicamycin or in knockout XBP-1 (a transcription factor which mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects of osteocalcin were nullified by suppression of Akt, mammalian target of rapamycin (mTOR) or nuclear factor kappa B (NFκB), suggesting that osteocalcin inhibits autophagy, ER stress and improves insulin signaling in the vascular tissue and cells under insulin resistance in a NFκB-dependent manner, which may be a promising therapeutic strategies of cardiovascular dysfunction secondary to obesity.

  7. 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.

  8. Bone turnover in passive smoking female rat: relationships to change in bone mineral density

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    Xu Wen-shuo

    2011-06-01

    Full Text Available Abstract Background Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD and bone turnover and the relationship between BMD and bone turnover in female rat. Methods Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP and Tartrate-resistant acid phosphatase 5b (TRACP 5b. BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027 and femur(r = 0.899, P = 0.002 in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005 and femur (r = -0.715, P = 0.046 in 4-month smoke-exposed female rats. Conclusion Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat.

  9. Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

    Science.gov (United States)

    Rosa, Brielle V; Blair, Hugh T; Vickers, Mark H; Dittmer, Keren E; Morel, Patrick C H; Knight, Cameron G; Firth, Elwyn C

    2013-01-01

    Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively). At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01) and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02); however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during pregnancy can

  10. Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

    Directory of Open Access Journals (Sweden)

    Brielle V Rosa

    Full Text Available Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively. At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01 and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02; however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during

  11. Low bone mass in microscopic colitis

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    Lakatos Péter

    2011-05-01

    Full Text Available Abstract Background Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. Aims The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. Methods Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively were measured using immunoassays. Results Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p 2; p 2. Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p Conclusions Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

  12. Zinc enhances bone metabolism in ovariectomized rats and exerts anabolic osteoblastic/adipocytic marrow effects ex vivo.

    Science.gov (United States)

    Li, Binbin; Liu, Hao; Jia, Shengnan

    2015-02-01

    Investigations of bone mass and marrow adiposity are critical for defining the role of zinc (Zn) in bone metabolism. Rats used for study were grouped as follows: control (sham), ovariectomy (OVX), ovariectomy + estradiol (OVX-E), ovariectomy + Zn treatment (OVX-Zn). Bone mineral density (BMD) was quantified (microCT); serum osteocalcin, adiponectin, RANKL, and TRAP levels were assayed (ELISA); and biochemical determinations of serum alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were done. Cells derived from bone mesenchymal stem cell (BMSC) isolates of respective test groups were compared, identifying primary osteoblasts by MTT assay and adipocytes by Oil Red O stain. Osteocalcin and adiponectin levels in culture supernatants were determined by ELISA. Zn supplementation resulted in a modest increase in BMD, but serum osteocalcin and ALP activity increased significantly (P < 0.01, both). Serum levels of RANKL and TRAP were lower in OVX-Zn (vs OVX) rats (P < 0.01), whereas serum concentrations of adiponectin, Ca, and P did not differ by group. Osteocalcin level was significantly upregulated ex vivo (P < 0.01) in the supernatant of cultured OVX-Zn (vs OVX) cells, accompanied by a slight upturn in osteoblastic differentiation. However, Oil Red O uptake and adiponectin level in supernatant were sharply diminished in cultured OVX-Zn (vs OVX) cells (P < 0.01). Overall, we concluded that Zn contributes to bone mass by marginally stimulating differentiation and proliferation of osteoblasts and by effectively inhibiting osteoclastic and adipocytic differentiation of BMSCs.

  13. Bone scan

    Science.gov (United States)

    ... legs, or spine fractures) Diagnose a bone infection (osteomyelitis) Diagnose or determine the cause of bone pain, ... 2015:chap 43. Read More Broken bone Metabolism Osteomyelitis Review Date 12/10/2015 Updated by: Jatin ...

  14. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  15. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  16. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  17. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    Science.gov (United States)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

  18. Interferon-γ plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice.

    Science.gov (United States)

    Duque, Gustavo; Huang, Dao Chao; Dion, Natalie; Macoritto, Michael; Rivas, Daniel; Li, Wei; Yang, Xian Fang; Li, Jiarong; Lian, Jing; Marino, Faleh Tamim; Barralet, Jake; Lascau, Viorica; Deschênes, Claire; Ste-Marie, Louis-Georges; Kremer, Richard

    2011-07-01

    Interferon γ (IFN-γ) is a cytokine produced locally in the bone microenvironment by cells of immune origin as well as mesenchymal stem cells. However, its role in normal bone remodeling is still poorly understood. In this study we first examined the consequences of IFN-γ ablation in vivo in C57BL/6 mice expressing the IFN-γ receptor knockout phenotype (IFNγR1(-/-)). Compared with their wild-type littermates (IFNγR1(+/+)), IFNγR1(-/-) mice exhibit a reduction in bone volume associated with significant changes in cortical and trabecular structural parameters characteristic of an osteoporotic phenotype. Bone histomorphometry of IFNγR1(-/-) mice showed a low-bone-turnover pattern with a decrease in bone formation, a significant reduction in osteoblast and osteoclast numbers, and a reduction in circulating levels of bone-formation and bone-resorption markers. Furthermore, administration of IFN-γ (2000 and 10,000 units) to wild-type C57BL/6 sham-operated (SHAM) and ovariectomized (OVX) female mice significantly improved bone mass and microarchitecture, mechanical properties of bone, and the ratio between bone formation and bone resorption in SHAM mice and rescued osteoporosis in OVX mice. These data therefore support an important physiologic role for IFN-γ signaling as a potential new anabolic therapeutic target for osteoporosis.

  19. Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats.

    Science.gov (United States)

    Tsirella, E; Mavrakanas, T; Rager, O; Tsartsalis, S; Kallaras, K; Kokkas, B; Mironidou-Tzouveleki, M

    2012-04-01

    Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

  20. Failure to Generate Bone Marrow Adipocytes Does Not Protect Mice from Ovariectomy-Induced Osteopenia

    Science.gov (United States)

    Iwaniec, Urszula T.; Turner, Russell T.

    2012-01-01

    A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kitW/W-v) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kitW/W-v mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kitW/W-v mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kitW/W-v mice. However, ovx in WT and kitW/W-v mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice. PMID:23246792

  1. Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults

    Directory of Open Access Journals (Sweden)

    Georgia Colleluori

    2017-01-01

    Full Text Available Background. Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods. One hundred seven frail, obese older adults were randomized into the control (N=27, diet (N=26, exercise (N=26, and diet-exercise (N=28 groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI. Results. UcOC increased in the diet group (36 ± 11.6% but not in the other groups (P<0.05 between groups. Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4% than in the diet group (61.9 ± 15.3% at 12 months (P<0.05. UcOC and body composition changes predicted DI variation in the diet group only (R2=0.712, while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2=0.140 and 0.107 and diet-exercise (∆R2=0.427 and 0.243 groups (P<0.05 for all. Conclusions. Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

  2. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    Science.gov (United States)

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (Pacid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage.

  3. Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

    Science.gov (United States)

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2017-04-04

    Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

  4. Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

    Science.gov (United States)

    Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

    2016-01-01

    This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations.

  5. Effect of Simvastatin collagen graft on wound healing of defective bone

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jun Ho; Kim, Gyu Tae [Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); Choi, Yong Suk; Lee, Hyeon Woo; Hwang, Eui Hwan [Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    2008-09-15

    To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

  6. Bone Formation with Deproteinized Bovine Bone Mineral or Biphasic Calcium Phosphate in the Presence of Autologous Platelet Lysate: Comparative Investigation in Rabbit

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    Carole Chakar

    2014-01-01

    Full Text Available Bone substitutes alone or supplemented with platelet-derived concentrates are widely used to promote bone regeneration but their potency remains controversial. The aim of this study was, therefore, to compare the regenerative potential of preparations containing autologous platelet lysate (APL and particles of either deproteinized bovine bone mineral (DBBM or biphasic calcium phosphate (BCP, two bone substitutes with different resorption patterns. Rabbit APL was prepared by freeze-thawing a platelet suspension. Critical-size defects in rabbit femoral condyle were filled with DBBM or DBBM+APL and BCP or BCP+APL. Rabbits were sacrificed after six weeks and newly formed bone and residual implanted material were evaluated using nondemineralized histology and histomorphometry. New bone was observed around particles of all fillers tested. In the defects filled with BCP, the newly formed bone area was greater (70%; P<0.001 while the residual material area was lower (60%; P<0.001 than that observed in those filled with DBBM. New bone and residual material area of defects filled with either APL+DBBM or APL+BCP were similar to those observed in those filled with the material alone. In summary, osteoconductivity and resorption of BCP were greater than those of DBBM, while APL associated with either DBBM or BCP did not have an additional benefit.

  7. PROTECTIVE EFFECT OF VITAMIN D3 IN METHYLPREDNISOLONE ACETATE (MPA INDUCED LOSS OF BONE METABOLISM MARKERS AND BONE MINERAL DENSITY IN THE LUMBAR SPINE OF RAT

    Directory of Open Access Journals (Sweden)

    I. Ragerdi-Kashani

    2007-05-01

    Full Text Available Although some vitamins have been shown to prevent glucocorticoids induced osteoporosis in short time, the magnitude of this effect remains to be clarified. The aim of this study was to evaluate protective effect of vitamin D3 on methylprednisolone acetate (MPA induced osteoporosis in rats. Twenty-four male Sprague Dawley rats were randomly divided into four groups: Group A (n = 6, was a base line control or normal animals. Group B (n = 6, was treated only normal saline, group C (n = 6, was treated MPA (0.2 mg/kg subcutaneously for 4 weeks (3 times per a week and finally group D (n = 6 were administered MPA resemble to group C and treated by Vitamin D3 (0.1 µg/kg dissolved in ethanol daily. Level of calcium, osteocalcin and acid phosphatase in serum were measured before and after treatment. Also, bone mineral density (BMD of lumber vertebrae was measured by dual energy X-ray absorptiometry. The results showed that the serum calcium level unaffected by MPA in all groups before and after treatment, but the serum osteocalcin level and bone mineral density of lumbar vertebrae were significantly (P < 0.05 decreased in group C compared with groups A and B. In group D serum osteocalcin level increased again significantly (P < 0.05 but increasing of BMD and bone mineral content were not significant. The findings indicate that by using of vitamin D3 in MPA treated rats could increase bone formation and decrease bone resorption.

  8. 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.

  9. Implant design and its effects on osseointegration over time within cortical and trabecular bone.

    Science.gov (United States)

    Beutel, Bryan G; Danna, Natalie R; Granato, Rodrigo; Bonfante, Estevam A; Marin, Charles; Tovar, Nick; Suzuki, Marcelo; Coelho, Paulo G

    2016-08-01

    Healing chambers present at the interface between implant and bone have become a target for improving osseointegration. The objective of the present study was to compare osseointegration of several implant healing chamber configurations at early time points and regions of interest within bone using an in vivo animal femur model. Six implants, each with a different healing chamber configuration, were surgically implanted into each femur of six skeletally mature beagle dogs (n = 12 implants per dog, total n = 72). The implants were harvested at 3 and 5 weeks post-implantation, non-decalcified processed to slides, and underwent histomorphometry with measurement of bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) within healing chambers at both cortical and trabecular bone sites. Microscopy demonstrated predominantly woven bone at 3 weeks and initial replacement of woven bone by lamellar bone by 5 weeks. BIC and BAFO were both significantly increased by 5 weeks (p < 0.001), and significantly higher in cortical than trabecular bone (p < 0.001). The trapezoidal healing chamber design demonstrated a higher BIC than other configurations. Overall, a strong temporal and region-specific dependence of implant osseointegration in femurs was noted. Moreover, the findings suggest that a trapezoidal healing chamber configuration may facilitate the best osseointegration. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1091-1097, 2016.

  10. X-ray microtomography of bones and teeth.

    Science.gov (United States)

    Davis, G R; Wong, F S

    1996-08-01

    X-ray microtomography is a miniaturized version of computerized axial tomography with a resolution of the order of micrometres. In the biomedical field it is particularly useful in the study of hard tissue because of its ability to accurately measure the linear attenuation coefficient. From this, the mineral concentration can be computed, which is one measure of bone quality. Using microtomography it is also possible to form three-dimensional images of bone from which structural parameters can be derived which could not be measured using conventional histomorphometry. Various types of microtomography scanner have been used, including simple translate-rotate systems which are capable of measuring x-ray attenuation at multiple energies simultaneously, and "cone-beam' systems which can acquire the necessary data for three-dimensional reconstructions in a relatively short time. Both laboratory x-ray sources and synchrotrons have been used in the study of hard tissue using microtomography. Most studies of bone have been concerned primarily with either the mineral concentration in cortical bone or the structure in cancellous bone. The mineral concentration in teeth has also been studied, in particular the loss of mineral in enamel during in vitro demineralization and the gain during subsequent remineralization. Although there are currently relatively few centres carrying out this work, interest in the technique is rapidly growing and it is likely to find a useful place both in research and ultimately in clinical practice.

  11. Fate of monocortical bone blocks grafted in the human maxilla: a histological and histomorphometric study.

    Science.gov (United States)

    Zerbo, Ilara R; de Lange, Gert L; Joldersma, Manon; Bronckers, Antonius L J J; Burger, Elisabeth H

    2003-12-01

    Local bone defects in the anterior maxilla are commonly grafted with monocortical blocks of autologous bone in order to restore the defect site prior to the placement of dental implants. Increasing evidence suggests that osteocytes are involved in the control of bone remodelling and thus may be important for optimalisation of bone structure around implants, and thus for implant osseointegration. However, it is not well known whether osteocytes will survive when bone blocks are grafted into defects. We grafted 19 patients with monocortical bone blocks derived from the symphysis, to the defect site in the maxillary alveolar process. The bone grafts were left to heal for times varying from 2.5 to 7 months. During implant installation, bone biopsies were removed using a trephine burr, and processed for hard tissue histology. Bone histology and histomorphometry were then carried out in order to gain insight into the density, viability and remodelling of the graft. Clinically, all the bone grafts were successful, with no implant failures, and little resorption was seen. Histologically, bone volume expressed as percentage of tissue volume at the implant site varied from 27% to 57% with an overall average of 41%. Bone fields with empty osteocyte lacunae were observed and measured. The amount of this so-called nonvital bone (NVB) varied between 1% and 34% of the total tissue volume. The amount of NVB decreased significantly with the time of healing. The data suggest that the majority of the osteocytes of the monocortical bone do not survive grafting. The results indicate that the NVB is progressively remodelled into new vital bone 7 months after grafting.

  12. Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats.

    Science.gov (United States)

    Isogai, Yukihiro; Takao-Kawabata, Ryoko; Takakura, Aya; Sugimoto, Emika; Nakazono, Osamu; Ikegaki, Ichiro; Kuriyama, Hiroshi; Ishizuya, Toshinori

    2015-10-01

    Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats. The amount of serum osteocalcin, a bone formation marker, was transiently reduced after single TPTD administration, but increased thereafter, remaining increased for several days. In contrast, the amount of excreted urinary C-telopeptide, a bone resorption marker, increased transiently after single TPTD administration, and subsequently returned to control levels on the day after administration. Tissue histomorphometric analyses conducted 8 h after administration showed no changes in bone formation or bone resorption parameters. However, at 48 h, the bone formation parameters OS/BS and Ob.S/BS were increased, while the bone resorption parameter ES/BS was decreased. After repeated TPTD administration for 4 weeks, OS/BS, Ob.S/BS, and MS/BS increased, while Oc.S/BS decreased. Serum osteocalcin at 4 weeks after repeated administration was significantly correlated with OS/BS and Ob.S/BS. These present findings indicate that TPTD has dual, time-dependent effects on bone resorption and bone formation. Immediately after single administration, there was transient promotion of bone resorption and suppression of bone formation. However, sustained stimulation of bone formation occurred thereafter. Furthermore, these data suggest that this sustained bone formation led to anabolic effects with repeated TPTD administration.

  13. Consumption of legumes improves certain bone markers in ovariectomized rats.

    Science.gov (United States)

    Lee, Sun Hee; Jin, Na; Paik, Doo-Jin; Kim, Deog-Yoon; Chung, Ill-Min; Park, Yongsoon

    2011-05-01

    Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17β-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats.

  14. Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

    Science.gov (United States)

    Sibonga, J. D.; Iwaniec, U.; Wu, H.

    2011-01-01

    PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal

  15. Quantification of bone mineral density to define osteoporosis in rat.

    Science.gov (United States)

    Srivastava, M; Mandal, S K; Sengupta, S; Arshad, M; Singh, M M

    2008-05-01

    The diagnosis of osteoporosis centers on assessment of bone mass and quality. In the absence of evidence-based guidelines to assess bone status in laboratory animals and unsuitability of use of T-/Z-scores meant for clinical application in animal studies, most investigators involved in new drug research and development employ clinical biomarkers and kits to assess bone turnover rate and portray change in bone mineral density (BMD) as percentage of increase/decrease, making comparative assessment of the effect highly impractical. This study proposes threshold boundaries of BMD (rT-score) in colony-bred Sprague-Dawley rats, distinct from those used clinically. Boundaries were obtained keeping fixed Type-I error (alpha=0.025). Femur neck was considered best for defining bone status using BMD measured by dual-energy X-ray absorptiometry. Findings demonstrate that BMD-1.96 and <-0.80 rT-score as osteopenia. Performance of boundaries to ascertain bone status was examined through simulation under different physiological/ hormonal states viz. estrogen deficiency, ageing, estrus cycle, pregnancy, and lactation. The Area Under the Receiver Operating Characteristic curve of 0.98 obtained using BMD of femur neck, being close to unity, shows excellent ability of the proposed rT-score to effectively identify osteoporosis. Further studies using certain hierarchical measures of bone quality such as histomorphometry, mechanical testing etc. could supplement these findings. Since, unlike humans, most laboratory animals including rats only exhibit osteopenia and do not fracture their bones, the proposed thresholds are intended to serve as categorical tools to define bone quality and not to predict fracture risk.

  16. Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

    Science.gov (United States)

    Li, Feng; Wang, Xujun; Niyibizi, Christopher

    2010-01-01

    Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

  17. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  18. Relative and combined effects of ethanol and protein deficiency on bone manganese and copper.

    Science.gov (United States)

    González-Pérez, José M; González-Reimers, Emilio; DeLaVega-Prieto, María José; Durán-Castellón, María del Carmen; Viña-Rodríguez, José; Galindo-Martín, Luis; Alvisa-Negrín, Julio; Santolaria-Fernández, Francisco

    2012-06-01

    Both manganese and copper may affect bone synthesis. Bone content of both metals can be altered in alcoholics, although controversy exists regarding this matter. To analyse the relative and combined effects of ethanol and a low protein diet on bone copper and manganese, and their relationships with bone structure and metabolism, including trabecular bone mass (TBM), osteoid area (OA), osteocalcin (OCN), insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), urinary hydroxyproline (uHP) and vitamin D. Adult male Sprague-Dawley rats were divided into four groups. The control rats received a 18% protein-containing diet; a second group, an isocaloric, 2% protein-containing diet; a third one, an isocaloric, 36% ethanol-containing diet and a fourth, an isocaloric diet containing 2% protein and 36% ethanol. After sacrifice, TBM and OA were histomorphometrically assessed; bone and serum manganese and copper were determined by atomic absorption spectrophotometry, and serum OCN, IGF-1, PTH, uHP and vitamin D by radioimmunoassay. Ethanol-fed rats showed decreased TBM and bone manganese. Significant relationships existed between bone manganese and TBM, serum IGF-1 and OCN. Ethanol leads to a decrease in bone manganese, related to decreased bone mass and bone synthesis. No alterations were found in bone copper.

  19. Production of New Trabecular Bone in Osteopenic Ovariectomized Rats by Prostaglandin E2

    Science.gov (United States)

    Mori, S.; Jee, W. S. S.; Li, X. J.

    1992-01-01

    Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3 month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1,3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4 month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg (PGE2)/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

  20. Bone sparing effect of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    Duangrat Tantikanlayaporn

    Full Text Available Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. Recently, an active phytoestrogen from Curcuma comosa Roxb, diarylheptanoid (DPHD, (3R-1,7-diphenyl-(4E,6E-4,6-heptadien-3-ol, was found to strongly promote human osteoblast function in vitro. In the present study, we demonstrated the protective effect of DPHD on ovariectomy-induced bone loss (OVX in adult female Sprague-Dawley rats with 17β-estradiol (E2, 10 µg/kg Bw as a positive control. Treatment of OVX animals with DPHD at 25, 50, and 100 mg/kg Bw for 12 weeks markedly increased bone mineral density (BMD of tibial metaphysis as measured by peripheral Quantitative Computed Tomography (pQCT. Histomorphometric analysis of bone structure indicated that DPHD treatment retarded the ovariectomy-induced deterioration of bone microstructure. Ovariectomy resulted in a marked decrease in trabecular bone volume, number and thickness and these changes were inhibited by DPHD treatment, similar to that seen with E2. Moreover, DPHD decreased markers of bone turnover, including osteocalcin and tartrate resistant acid phosphatase (TRAP activity. These results suggest that DPHD has a bone sparing effect in ovariectomy-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, DPHD appears to be a promising candidate for preserving bone mass and structure in the estrogen deficient women with a potential role in reducing postmenopausal osteoporosis.

  1. PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

    Directory of Open Access Journals (Sweden)

    Karsdal Morten A

    2009-12-01

    Full Text Available Abstract Background Bone size (BS variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1 locus. Carriers of the major A allele of the most significant polymorphism, rs7595412, have around 17% larger hip BS than non-carriers. We therefore hypothesized that this polymorphism may also influence postmenopausal complications. Methods The effects of rs7595412 on hip BS, bone mineral density (BMD, vertebral fractures, serum Crosslaps and osteocalcin levels were analyzed in 1,191 postmenopausal Danish women. Results This polymorphism had no influence on hip and spine BS as well as on femur and spine BMD. Women carrying at least one copy of the A allele had lower levels of serum osteocalcin as compared with those homozygous for the G allele (p = 0.03 whereas no effect on serum Crosslaps was detected. Furthermore, women homozygous for the A allele were more affected by vertebral fractures than those carrying at least one copy of the G allele (p = 0.04. Conclusions In postmenopausal women, our results suggest that the PLCL1 rs7595412 polymorphism has no obvious effect on hip BS or BMD but may be nominally associated with increased proportion of vertebral fracture and increased levels of osteocalcin.

  2. Disruption of BMP Signaling in Osteoblasts Through Type IA Receptor (BMPRIA) Increases Bone Mass*

    Science.gov (United States)

    Kamiya, Nobuhiro; Ye, Ling; Kobayashi, Tatsuya; Lucas, Donald J; Mochida, Yoshiyuki; Yamauchi, Mitsuo; Kronenberg, Henry M; Feng, Jian Q; Mishina, Yuji

    2008-01-01

    Bone morphogenetic proteins (BMPs) are known as ectopic bone inducers. The FDA approved BMPs (BMP2 and BMP7) for clinical use. However, direct effects of BMPs on endogenous bone metabolism are not yet well known. We conditionally disrupted BMP receptor type IA (BMPRIA) in osteoblasts during weanling and adult stages to show the impact of BMP signaling on endogenous bone modeling and remodeling. Cre recombination was detected in immature osteoblasts in the periosteum, osteoblasts, and osteocytes but not in chondrocytes and osteoclasts after tamoxifen administration. Bmpr1a conditional knockout mice (cKO) showed increased bone mass primarily in trabecular bone at P21 and 22 wk as determined by H&E staining. Vertebrae, tails, and ribs showed increased radiodensity at 22 wk, consistent with a significant increase in BMD. Both μCT and histomorphometry showed an increase in trabecular BV/TV and thickness of cKO adult bones, whereas osteoclast number, bone formation rate, and mineral apposition rate were decreased. Expression levels of bone formation markers (Runx2 and Bsp), resorption markers (Mmp9, Ctsk, and Tracp), and Rankl were decreased, and Opg was increased in adult bones, resulting in a reduction in the ratio of Rankl to osteoprotegerin (Opg). The reduction in osteoclastogenesis through the RANKL–OPG pathway was also observed in weanling stages and reproduced in newborn calvaria culture. These results suggest that Bmpr1a cKO increased endogenous bone mass primarily in trabecular bone with decreased osteoclastogenesis through the RANKL–OPG pathway. We conclude that BMPRIA signaling in osteoblasts affects both bone formation and resorption to reduce endogenous bone mass in vivo. PMID:18684091

  3. Disruption of BMP signaling in osteoblasts through type IA receptor (BMPRIA) increases bone mass.

    Science.gov (United States)

    Kamiya, Nobuhiro; Ye, Ling; Kobayashi, Tatsuya; Lucas, Donald J; Mochida, Yoshiyuki; Yamauchi, Mitsuo; Kronenberg, Henry M; Feng, Jian Q; Mishina, Yuji

    2008-12-01

    Bone morphogenetic proteins (BMPs) are known as ectopic bone inducers. The FDA approved BMPs (BMP2 and BMP7) for clinical use. However, direct effects of BMPs on endogenous bone metabolism are not yet well known. We conditionally disrupted BMP receptor type IA (BMPRIA) in osteoblasts during weanling and adult stages to show the impact of BMP signaling on endogenous bone modeling and remodeling. Cre recombination was detected in immature osteoblasts in the periosteum, osteoblasts, and osteocytes but not in chondrocytes and osteoclasts after tamoxifen administration. Bmpr1a conditional knockout mice (cKO) showed increased bone mass primarily in trabecular bone at P21 and 22 wk as determined by H&E staining. Vertebrae, tails, and ribs showed increased radiodensity at 22 wk, consistent with a significant increase in BMD. Both muCT and histomorphometry showed an increase in trabecular BV/TV and thickness of cKO adult bones, whereas osteoclast number, bone formation rate, and mineral apposition rate were decreased. Expression levels of bone formation markers (Runx2 and Bsp), resorption markers (Mmp9, Ctsk, and Tracp), and Rankl were decreased, and Opg was increased in adult bones, resulting in a reduction in the ratio of Rankl to osteoprotegerin (Opg). The reduction in osteoclastogenesis through the RANKL-OPG pathway was also observed in weanling stages and reproduced in newborn calvaria culture. These results suggest that Bmpr1a cKO increased endogenous bone mass primarily in trabecular bone with decreased osteoclastogenesis through the RANKL-OPG pathway. We conclude that BMPRIA signaling in osteoblasts affects both bone formation and resorption to reduce endogenous bone mass in vivo.

  4. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

    Science.gov (United States)

    Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2016-10-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

  5. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  6. Changes in mechanical properties of bone within the mandibular condyle with age.

    Science.gov (United States)

    Huja, Sarandeep S; Rummel, Andrew M; Beck, Frank M

    2008-02-01

    The purpose of the study was to compare indentation modulus (IM) and hardness of condylar bone in young and adult dogs. In addition we desired to examine histologic sections for bone formation activity in the two groups. Mandibular condyles were obtained from adult (1- to 2-year-old) and young (approximately 5-m old) dogs. Two sections/condyle were obtained and one was processed for histomorphometry and the other for mechanical analyses. Indents were made on moist condylar trabecular bone to a depth of 500 nm at a loading rate of 10 nm/s using a custom-made hydration system to obtain IM and hardness. Histomorphometric analyses measured the bone volume/total volume (BV/TV%) and ratio of labeled to unlabeled bone within the condyle. Data were analyzed using a repeated-measures factorial analysis of variance and Tukey-Kramer method. Overall, the IM of the adult condyles (10.0+/-3.4 GPa, Mean+/-SD) were significantly (Pcondylar bone suggested higher bone forming activity than in adult condyles (27.5%). With age there is a change in mass and material properties in the trabecular bone of the mandibular condyle in dogs.

  7. Melatonin dietary supplement as an anti-aging therapy for age-related bone loss.

    Science.gov (United States)

    Tresguerres, Isabel F; Tamimi, Faleh; Eimar, Hazem; Barralet, Jake E; Prieto, Santiago; Torres, Jesús; Calvo-Guirado, José Luis; Tresguerres, Jesús A F

    2014-08-01

    Previous studies have shown that melatonin, an anti-oxidant molecule secreted from the pineal gland, is a positive regulator of bone mass. However, the potential effects of melatonin on bone mass have never been investigated in an old population. The aim of this study was to assess the effects of dietary melatonin supplementation on mass accrual and biomechanical properties of old rat femora. Twenty 22-month-old male Wistar rats were divided into two randomly assigned groups. The first group was treated for 10 weeks with melatonin, whereas the second group was untreated (control). Rat femurs were collected, and their phenotypes and biomechanical properties were investigated by micro-computed tomography, histomorphometry, and a three-point-bending test. Statistical analyses were performed by the Student two-tailed unpaired t-test. In all experiments, a value of p<0.05 was considered significant. Rats treated with melatonin had higher bone volume, bone trabecular number, trabecular thickness, and cortical thickness in comparison to the control group. Histomorphometric analyses confirmed the increase of bone volume in melatonin-treated rats. In agreement with these findings, melatonin-treated rats showed higher bone stiffness, flexural modulus, and ultimate load compared to controls. These compelling results are the first evidence indicating that dietary melatonin supplementation is able to exert beneficial effects against age-related bone loss in old rats, improving the microstructure and biomechanical properties of aged bones.

  8. Role of Soy Protein on Bone Turnover

    Directory of Open Access Journals (Sweden)

    A Haghighian roudsari

    2004-03-01

    Full Text Available Bone mass loss is one of the commonest menopause symptoms, resulting from cessation of estrogen production. Compounds which have estrogen – like biological activity similar to “Isoflavones” present in plants especially soy, may reduce bone loss in postmenopausal women, because as they are similar in structure to estrogens. This study, therefore, was undertaken to assess the effect of soy protein on bone metabolism biomarkers in postmenopausal women with osteopenia. This “before and after” clinical trial was carried out, on 15 postmenopausal women with osteopenia, between 45 to 64 years of age. The subjects were asked to consume 35 gram/day of soy protein for 12 weeks. Blood and urine samples, were taken at 0, 6 and 12 weeks of the study. Anthropometric measurements and a 2-day dietary recall were done at the beginning of the study, and at the 6 and 12 weeks. The food consumption data were analyzed by “Food Proccessor” software. Repeated measurement analysis was utilized to determine the changes in biochemical indices, anthropometric and dietary data. P-values less than 0.05 were considered as significant. Comparison of weight, BMI, physical activity and dietary intake of subjects during the study did not show any significant differences. Soy protein consumption, showed significant reductions in deoxypyridinoline (biochemical marker of bone resorption and significant increase in total alkaline phosphatase ( biochemical marker of bone formation.There were no significant differences in serum osteocalcin, C- telopeptide, insulin- like growth factor binding protein 3 (IGFBP3, and type-I- collagen telopeptides. Considering the beneficial effects of soy protein consumption on bone metabolism biomarkers, inclusion of this inexpensive and available food item in postmenopausal women diet, may reduce bone loss and could be recommended for the prevention of osteoporosis.

  9. Role of Soy Protein on Bone Turnover

    Directory of Open Access Journals (Sweden)

    A Haghighian roudsari

    2004-11-01

    Full Text Available Bone mass loss is one of the commonest menopause symptoms, resulting from cessation of estrogen production. Compounds which have estrogen – like biological activity similar to “Isoflavones” present in plants especially soy, may reduce bone loss in postmenopausal women, because as they are similar in structure to estrogens. This study, therefore, was undertaken to assess the effect of soy protein on bone metabolism biomarkers in postmenopausal women with osteopenia. This “before and after” clinical trial was carried out, on 15 postmenopausal women with osteopenia, between 45 to 64 years of age. The subjects were asked to consume 35 gram/day of soy protein for 12 weeks. Blood and urine samples, were taken at 0, 6 and 12 weeks of the study. Anthropometric measurements and a 2-day dietary recall were done at the beginning of the study, and at the 6 and 12 weeks. The food consumption data were analyzed by “Food Proccessor” software. Repeated measurement analysis was utilized to determine the changes in biochemical indices, anthropometric and dietary data. P-values less than 0.05 were considered as significant. Comparison of weight, BMI, physical activity and dietary intake of subjects during the study did not show any significant differences. Soy protein consumption, showed significant reductions in deoxypyridinoline (biochemical marker of bone resorption and significant increase in total alkaline phosphatase ( biochemical marker of bone formation.There were no significant differences in serum osteocalcin, C- telopeptide, insulin- like growth factor binding protein 3 (IGFBP3, and type-I- collagen telopeptides. Considering the beneficial effects of soy protein consumption on bone metabolism biomarkers, inclusion of this inexpensive and available food item in postmenopausal women diet, may reduce bone loss and could be recommended for the prevention of osteoporosis.

  10. Estrogen modulates the mRNA levels for cancellous bone protein of ovariectomized rats.

    Science.gov (United States)

    Salih, M A; Liu, C C; Arjmandi, B H; Kalu, D N

    1993-12-01

    This study was undertaken to examine the effects of ovariectomy and 17 beta-estradiol (E2) on the gene expression of type 1 collagen, osteocalcin and the protooncogen, c-myc, in cancellous bone. Female Sprague-Dawley rats, aged 95 days, were divided into 4 groups. Group 1 was sham operated and Groups 2-4 were ovariectomized. Groups 3 and 4 received daily injections of 160 ng and 1600 ng E2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All animals were sacrificed after 14 days. The femurs were dissected out and cancellous bone scraped from the distal metaphysis. RNA was isolated from the cancellous bone, immobilized on filters or size-fractionated by agarose gel electrophoresis and adsorbed on filters which were then hybridized with specific cDNA probes. Ovariectomy resulted in a significant increase in the mRNAs of type 1 collagen, osteocalcin and c-myc. The increase was suppressed in animals that received 17 beta-estradiol injections. In addition, ovariectomy caused the expected decrease in cancellous bone in the proximal tibia and increased osteoclast and osteoblast numbers. The ovariectomy-induced changes were prevented by 17 beta-estradiol administration. These findings suggest that the lack of ovarian hormones shortly after ovariectomy up-regulates and estrogen administration down-regulates the expression of important cancellous bone matrix proteins as well as the protooncogen, c-myc.

  11. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    Science.gov (United States)

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

  12. ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells

    Science.gov (United States)

    Valabrega, G; Fagioli, F; Corso, S; Madon, E; Brach del Prever, A; Biasin, E; Linari, A; Aglietta, M; Giordano, S

    2003-01-01

    Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT–PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker. PMID:12569382

  13. The effects of n-3 long-chain polyunsaturated fatty acids on bone formation and growth factors in adolescent boys

    DEFF Research Database (Denmark)

    Damsgaard, C. T.; Mølgaard, C.; Gyldenløve, S. N.

    2012-01-01

    NTRODUCTION: Animal studies indicate that n-3 long-chain polyunsaturated fatty acids (LCPUFAs) increase bone formation. To our knowledge, no studies have examined this in growing humans. This study investigated whether bone mass and markers of bone formation and growth were (i) associated......), bone area (BA), bone mineral density (BMD), plasma osteocalcin, and growth factors were measured at wk 0 and wk 16, as well as diet, physical activity, and n-3 LCPUFA status in erythrocytes. RESULTS: Fish oil strongly increased DHA status (P = 0.0001). No associations were found between DHA status...... and BMC, BA, BMD, or the markers of bone formation and growth at baseline. Furthermore, the fish oil intervention did not affect any of the outcomes as compared with control. However, dose-response analyses revealed a positive association between changes in DHA status and plasma insulin-like growth factor...

  14. Prostaglandin E2 Increased Rat Cortical Bone Mass When Administered Immediately Following Ovariectomy

    Science.gov (United States)

    Ke, Hua Zhu; Jee, Webster S.S.; Zeng, Qing Qiang; Li, Mei; Lin, Bai Yun

    1993-01-01

    To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3 month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabmular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow

  15. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    Science.gov (United States)

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  16. Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells.

    Science.gov (United States)

    Shi, Jiajia; Sun, Jie; Zhang, Wen; Liang, Hui; Shi, Qin; Li, Xiaoran; Chen, Yanyan; Zhuang, Yan; Dai, Jianwu

    2016-10-07

    The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34(+) and c-kit(+) endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

  17. 血清骨钙素水平与老年骨质疏松及冠状动脉病变的相关性%Relations between serum levels of osteocalcin and the diseases of osteoporosis and coronary artery calcification in elderly men

    Institute of Scientific and Technical Information of China (English)

    卢维晟; 张江蓉; 高艳虹; 袁惠敏; 王一尘

    2013-01-01

    目的 探讨血清骨钙素水平与老年骨质疏松及冠状动脉病变的相关性.方法 选取183例年龄在60 ~ 85岁的患者,根据骨密度测定结果分为2组:非骨质疏松组86例,骨质疏松组97例;根据冠状动脉螺旋CT检查结果分为3组:轻度钙化组(积分<200)68例;中度钙化组(200≤积分<300)43例;重度钙化组(积分≥300)72例.比较各组患者的冠状动脉狭窄病变和钙化程度.应用酶联免疫吸附试验者测定各组患者血清骨钙素水平.结果 骨质疏松组患者合并肥胖、高血压、高血脂和糖尿病的比例分别为56.7%(55/97)、80.4%(78/97)、78.4%(76/97)、71.1% (69/97),高于非骨质疏松组的37.2% (32/86)、54.7%(47/86)、44.2%(38/86)、31.4%(27/86)(P<0.05);骨质疏松组患者血清骨钙素水平明显低于非骨质疏松组患者[(14±3)ng/L比(42±6)ng/L(P <0.05)];骨质疏松组患者任意冠状动脉分支的钙化程度均高于非骨质疏松组,2组比较差异有统计学意义(P<0.05).骨质疏松组冠状动脉单支病变超过50%狭窄者比例明显高于非骨质疏松组,冠状动脉2支以上病变者占比更高[20.6% (20/97)比3.5% (3/86)],差异均有统计学意义(均P<0.05).冠状动脉血清骨钙素水平分别为(45.6±8.3)、(26.2±4.8)、(15.5±10.2) ng/L,任意两两比较差异均有统计学意义(均P<0.01).结论 骨钙流失与钙质在冠状动脉的沉积存在共同的发病机制.该机制与血清骨钙素水平有关,血清骨钙素对老年男性骨质疏松与冠状动脉钙化有保护作用.%Objective To determine osteocalcin in serum in elderly man; to discuss the effects of abnormal calcium metabolism between osteoporosis and coronary artery calcification in elderly men.Methods According to the results of the bone density,183 patients with an age from 60 to 85 (72 ± 8.8),were divided into two groups:non-osteoporosis group(n =86) and osteoporosis group(n =97).According to the

  18. Comments on: Effects of Wi-Fi (2.45 GH z Exposure on Apoptosis, Sperm Parameters and Testicular Histomorphometry in Rats: A Time Course Study

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Javad Mortazavi

    2016-02-01

    Full Text Available We read with great interest an article by Shokri et al. entitled "Effects of Wi-Fi (2.45 GH z exposure on apoptosis, sperm parameters and testicular histomorphometry in rats: a time course study" that is published in the latest issue of the Cell Journal (Vol.17, 2015: 322-331. In this article, Shokri et al. have presented their findings obtained in an experiment on an animal model. These researchers exposed rats to the 2.45 GHz radiation in a chamber with two Wi-Fi antennas on opposite walls of a box. The exposed animals in this study showed a decrease in sperm parameters. We have previously shown that exposure to electromagnetic fields generated by Wi-Fi routers or mobile phone jammers can adversely affect the sperm quality (1-3. The paper published by Shokri et al. is seriously flawed. The first major shortcoming of this paper is its exposure geometry. The authors stated that their exposure system was "a chamber (180 cm×80 cm×70 cm, designed for whole-body exposure of free-moving rats to a Wi-Fi signal. Two Wi-Fi antennas (NanoStation Loco M2, 2.45 GHz, 8.5 dBi, Ubiquiti Networks, Inc. USA were placed at the center of two sides of the chamber". It should be noted that in this case, the power density can be calculated using the below equation: S=P•G/4πR2 Where S=Power density P=Power input to antenna G=Antenna gain In this light, the geometry used in the study of Shokri et al. makes a very inhomogeneous distribution of power densities. The second shortcoming comes from this point that the authors claimed that their study was performed on a basis that could not affect the hormonal balance "A previous study applied a restrainer to fix space between antenna and rat. Since it was a stressful condition that could probably affect hormonal balance of animals, we tried to assess the effect of radiation on the free moving animals". However, these authors only had a control group and did not use a sham-exposed group to control the animals’s stress

  19. Influence of laser photobiomodulation (GaAlAs) on salivary flow rate and histomorphometry of the submandibular glands of hypothyroid rats.

    Science.gov (United States)

    de Jesus, Vivianne Cruz; Beanes, Graziele; Paraguassú, Gardênia Matos; Ramalho, Luciana Maria Pedreira; Pinheiro, Antônio Luiz Barbosa; Ramalho, Maria José Pedreira; Rodriguez, Tania Tavares

    2015-05-01

    The aim of this study was to analyze the influence of laser photobiomodulation in salivary flow, weight, and histomorphometry of the submandibular glands of hypothyroid rats. Fifty-six male Wistar albino rats were divided in euthyroid group and hypothyroid group, treated with propylthiouracil (PTU) to induce hypothyroidism. Each group was divided into control (without laser) and laser groups (GaAlAs): λ660 nm (40 mW), λ780 nm (40 mW), and λ780 nm (70 mW). The laser application on the submandibular gland occurred after 2 weeks of PTU treatment and repeatedly during 2 weeks every 48 h. The rats were anesthetized, tracheostomized, and the evaluation of the salivary flow rate (μL/min/100 g body weight) was made by the weight of the saliva collected for 15 min from the first drop. After the animals' death, the glands were dissected and processed for histological analysis. There was an evident reduction of the salivary flow of hypothyroid rats in all groups in comparison to euthyroid group (Mann-Whitney test, p photobiomodulation compared with their control groups. Histological analysis revealed a decrease in the parenchyma of the salivary glands of hypothyroid rats, but the laser was not able to reverse this process. Hypothyroid rats irradiated or not with laser showed acini and acinar cells with significantly smaller areas than euthyroid groups. The laser photobiomodulation protocol used was not able to change salivary flow or reverse the acinar atrophy process in the submandibular glands of hypothyroid rats.

  20. Effect of maternal use of flaxseed oil during pregnancy and lactation on glucose metabolism and pancreas histomorphometry of male offspring from diabetic rats.

    Science.gov (United States)

    Correia-Santos, André Manoel; Suzuki, Akemi; Vicente, Gabriela Câmara; Dos Anjos, Juliana Saraiva; Pereira, Aline D'Avila; Lenzi-Almeida, Kátia Calvi; Boaventura, Gilson Teles

    2014-12-01

    Investigate if the maternal use of flaxseed oil prevents pancreatic alterations in the offspring of diabetic mothers. Diabetes was induced in female wistar rats (n=12) by a high-fat diet and low-dose of streptozotocin. After the confirmation of the diabetes (glucose >300 mg/dL), rats were mated and once pregnancy was confirmed, they were allocated into three groups (n=6): high-fat group (HFG); flaxseed oil group (FOG); and control group (CG) (nondiabetic rats). At weaning, male offspring (n=12/group) received a standard chow diet. The animals were euthanized in two phases: at 100 and at 180 days, (n=6/group). The pancreas was collected for histomorphometric and immunohistochemistry analysis. HFG showed hypertrophy of pancreatic islets at 100 and at 180 days (p<0.0001), while the FOG offspring had islets with smaller diameters compared to HFG at both phases of sacrifice (p<0.0001). HFG had a lower percentage of small islets when compared to CG and FOG, which had a higher percentage when compared to HFG (p=0.0053) at 100 days. At 180 days HFG showed higher percentage of larger islets (p=0.00137) and lower percentage of smaller islets (p=0.00112), when compared to FOG. HFG showed lower islet insulin immunodensity at 100 days (p<0.0001) and 180 days (p<0.0001), whereas FOG was similar to CG (p<0.0001) at 100 days and higher at 180 days (p<0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycemia, promoting normal pancreas histomorphometry and β cell mass. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Pre-operative training induces changes in the histomorphometry and muscle function of the pelvic floor in patients with indication of radical prostatectomy.

    Science.gov (United States)

    Ocampo-Trujillo, A; Carbonell-González, J; Martínez-Blanco, A; Díaz-Hung, A; Muñoz, C A; Ramírez-Vélez, R

    2014-01-01

    To evaluate the efficacy of preoperative pelvic floor muscle training (PFMT) on histomorphometry, muscle function, urinary continence and quality of life of patients undergoing radical prostatectomy (RP). A prospective intervention clinical study was designed in 16 patients with indication of RP who were randomized into two groups. The Control Group received routine pre-surgical education (hygienic-dietary measures). The intervention group received a training session with supervised PFMT, three times a day, for four weeks, 30 days before the PR. Muscle function of the external urethral sphincter, contraction pressure of the levator ani, urinary continence and quality of life related to health (HRQoL) were evaluated before and after the intervention. At the end of the intervention and day of the surgery, samples of residual muscle tissue were obtained from the external sphincter muscle of the urethra for histomorphometric analysis. After the intervention, those participants who carried out PFMT showed an increase in the cross-sectional area of the muscle fibers of the external urethral sphincter (1,313 ± 1,075 μm(2)vs. 1,056 ± 844 μm(2), P=.03) and higher pressure contraction of the levator ani (F=9.188; P=.010). After catheter removal, 62% of patients in the experimental group and 37% in the control group showed no incontinence. After removal of the catheter, 75% of the experimental group did not require any pad compared to 25% in the control group (p=NS). There were no significant differences between the two groups in any of the HRQoL domains studied. Pre-surgical PFMT in patients with RP indication induces changes in the histology and function of the pelvic floor muscles, without changes in urogenital function and HRQoL. These results provide new evidence regarding the benefit of PFMT in preventing RP associated complications. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  2. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone.

    Directory of Open Access Journals (Sweden)

    Zhendong A Zhong

    Full Text Available The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1 and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.

  3. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone.

    Science.gov (United States)

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

    2015-01-01

    The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR) knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1) and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.

  4. Small intestine submucosa sponge for in vivo support of tissue-engineered bone formation in the presence of rat bone marrow stem cells.

    Science.gov (United States)

    Kim, Kyung Sook; Lee, Ju Young; Kang, Yun Mi; Kim, E Sle; Kim, Gyeong Hae; Rhee, Sang Dal; Cheon, Hyae Gyeong; Kim, Jae Ho; Min, Byoung-Hyun; Lee, Hai Bang; Kim, Moon Suk

    2010-02-01

    The aim of the current study was to visualize new bone formed in vivo on a small intestine submucosa (SIS) sponge used as a tissue-engineered scaffold for the repair of damaged bone. The SIS sponge provided a three-dimensional pore structure, and supported good attachment and viability of rat bone marrow stem cells (rBMSCs). To examine bone regeneration, we prepared full-thickness bilateral bone defects in the rat crania, and then treated the defects with an implanted SIS sponge or PGA mesh without or with rBMSCs, or left the defects untreated. Bone defects were evaluated by micro-CT and histologically after 2 and 4 weeks. Micro-CT demonstrated a trend toward a decrease in bone void in both the SIS sponge and SIS sponge/rBMSCs groups compared to the control and PGA mesh groups. At 4 weeks, bone formation in defects containing SIS sponge/rBMSCs was significantly greater than in all other groups. A histological analysis after 2 and 4 weeks of implantation showed localized collagen and osteocalcin deposition on SIS sponges and SIS sponges with rBMSCs. These in vivo results indicate that the SIS sponge, implanted at bone-removal defects, facilitated bone regeneration.

  5. Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation

    Directory of Open Access Journals (Sweden)

    AE Rapp

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSC were shown to support bone regeneration, when they were locally transplanted into poorly healing fractures. The benefit of systemic MSC transplantation is currently less evident. There is consensus that systemically applied MSC are recruited to the site of injury, but it is debated whether they actually support bone formation. Furthermore, the question arises as to whether circulating MSC are recruited only in case of injury or whether they also participate in mechanically induced bone formation. To answer these questions we injected green fluorescent protein (GFP-labelled MSC into C57BL/6J mice, which were subjected either to a femur osteotomy or to non-invasive mechanical ulna loading to induce bone formation. We detected GFP-labelled MSC in the early (day 10 and late fracture callus (day 21 by immunohistochemistry. Stromal cell-derived factor 1 (SDF-1 or CXCL-12, a key chemokine for stem cell attraction, was strongly expressed by virtually all cells near the osteotomy – indicating that SDF-1 may mediate cell migration to the site of injury. We found no differences in SDF-1 expression between the groups. Micro-computed tomography (µCT revealed significantly more bone in the callus of the MSC treated mice compared to untreated controls. The bending stiffness of callus was not significantly altered after MSC-application. In contrast, we failed to detect GFP-labelled MSC in the ulna after non-invasive mechanical loading. Histomorphometry and µCT revealed a significant load-induced increase in bone formation; however, no further increase was found after MSC administration. Concluding, our results suggest that systemically administered MSC are recruited and support bone formation only in case of injury but not in mechanically induced bone formation.

  6. Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

    Science.gov (United States)

    Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

    2017-12-01

    18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV50%). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

  7. Effects of short-term testosterone replacement on areal bone mineral density and bone turnover in young hypogonadal males

    Directory of Open Access Journals (Sweden)

    Prasun Deb

    2012-01-01

    Full Text Available Context: Effect of parenteral testosterone esters administration on bone-mineral density (BMD and bone turnover in young age onset male hypogonadism is not studied in Indian subjects. Aims: To prospectively study the effect of short-term (6 months replacement therapy with parenteral testosterone enanthate-propionate combination on BMD and bone turnover markers in hypogonadal adult patients. Settings and Design: Prospective, tertiary care academic center. Materials and Methods: Thirteen young, otherwise healthy hypogonadal males (age 25.5 ± 4.9 yrs, serum testosterone 2.56 ± 4.29 nmol/l were subjected to BMD measurements (DXA and estimation of urinary Crosslaps™ and serum osteocalcin at baseline. Twelve healthy age and BMI-matched males served as controls for BMD measurements. The hypogonadal patients were administered parenteral testosterone esters (as mixed enanthate and propionate 250 mg i.m. every 2-3 weeks, and prospectively followed for 6 months. BMD and bone markers were studied at the end of 6 months. Statistical Analysis Used: Mann-Whitney nonparametric test, paired t-test and Pearson′s test of two-tail significance. Results: At baseline, BMD was significantly lower in hypogonadal males as compared to that in controls. With testosterone replacement, there was significant improvement in BMD, both at trabecular and cortical sites, There was a decline in bone turnover with treatment (Ur Crosslaps™:creatinine ratio: pretreatment 72.8 ± 40.4, post-treatment 35.5 ± 23.8 μg/mmol, P = 0.098; serum osteocalcin: pre-treatment 41.0 ± 16.8, post-treatment 31.7 ± 2.1 ng/ml, P = 0.393. Conclusions: Short-term parenteral testosterone replacement significantly improves BMD at the hip, lumbar spine and forearm in hypogonadal young males.

  8. Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

    Science.gov (United States)

    Bilezikian, John P; Watts, Nelson B; Usiskin, Keith; Polidori, David; Fung, Albert; Sullivan, Daniel; Rosenthal, Norm

    2016-01-01

    Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM). Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM. This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension. This study was undertaken in 90 centers in 17 countries. Patients were aged 55-80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen. Canagliflozin 100 or 300 mg or placebo were administered once daily. BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 β-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52. Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: -0.9% and -1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 β-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol. In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.

  9. Paradoxical effects of partial leptin deficiency on bone in growing female mice.

    Science.gov (United States)

    Philbrick, Kenneth A; Turner, Russell T; Branscum, Adam J; Wong, Carmen P; Iwaniec, Urszula T

    2015-12-01

    Morbidly obese, leptin-deficient ob/ob mice display low bone mass, mild osteoclast-rich osteopetrosis, and increased bone marrow adiposity. While partial leptin deficiency results in increased weight, the skeletal manifestations of partial leptin deficiency are less well defined. We therefore analyzed femora and lumbar vertebrae in growing (7-week-old) female C57BL/6 wildtype (WT) mice, partial leptin-deficient ob/+ mice, and leptin-deficient ob/ob mice. The bones were evaluated by dual energy absorptiometry, microcomputed tomography and histomorphometry. As expected, ob/+ mice were heavier, had more white adipose tissue, and lower serum leptin than WT mice, but were lighter and had less white adipose tissue than ob/ob mice. With a few exceptions, cancellous bone architecture, cell (osteoblast, osteoclast, and adipocyte), and dynamic measurements did not differ between WT and ob/+ mice. In contrast, compared to WT and ob/+ mice, ob/ob mice had lower cancellous bone volume fraction, and higher bone marrow adiposity in the femur metaphysis, and higher cancellous bone volume fraction in lumbar vertebra. Paradoxically, ob/+ mice had greater femoral bone volume than either WT or ob/ob mice. There was a positive correlation between body weight and femur volume in all three genotypes. However, the positive effect of weight on bone occurred with lower body weight in leptin-producing mice. The paradoxical differences in bone size among WT, ob/+, and ob/ob mice may be explained if leptin, in addition to stimulating bone growth and cancellous bone turnover, acts to lower the set-point at which increased body weight leads to a commensurate increase in bone size. © 2015 Wiley Periodicals, Inc.

  10. Study of a new bone-targeting titanium implant–bone interface

    Directory of Open Access Journals (Sweden)

    Liu XN

    2016-11-01

    Full Text Available Xiangning Liu,1,* Ye Zhang,1,* Shaobing Li,2,* Yayu Wang,3 Ting Sun,1 Zejian Li,1 Lizhao Cai,1 Xiaogang Wang,3,* Lei Zhou,2 Renfa Lai1 1The Medical Center of Stomatology, The First Affiliated Hospital of Jinan University, 2The Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, 3Department of Cell Biology, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: New strategies involving bone-targeting titanium (Ti implant–bone interface are required to enhance bone regeneration and osseointegration for orthopedic and dental implants, especially in osteoporotic subjects. In this study, a new dual-controlled, local, bone-targeting delivery system was successfully constructed by loading tetracycline-grafted simvastatin (SV-loaded polymeric micelles in titania nanotube (TNT arrays, and a bone-targeting Ti implant–bone interface was also successfully constructed by implanting the delivery system in vivo. The biological effects were evaluated both in vitro and in vivo. The results showed that Ti surfaces with TNT–bone-targeting micelles could promote cytoskeletal spreading, early adhesion, alkaline phosphatase activity, and extracellular osteocalcin concentrations of rat osteoblasts, with concomitant enhanced protein expression of bone morphogenetic protein (BMP-2. A single-wall bone-defect implant model was established in normal and ovariectomized rats as postmenopausal osteoporosis models. Microcomputed tomography imaging and BMP-2 expression in vivo demonstrated that the implant with a TNT-targeting micelle surface was able to promote bone regeneration and osseointegration in both animal models. Therefore, beneficial biological effects were demonstrated both in vitro and in vivo, which indicated that the bone-targeting effects of micelles greatly enhance the

  11. Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate.

    Science.gov (United States)

    König, P; Hillman, L; Cervantes, C; Levine, C; Maloney, C; Douglass, B; Johnson, L; Allen, S

    1993-02-01

    Previous studies have shown that inhaled corticosteroids can affect bone metabolism in adults. A study to assess the effect of inhaled beclomethasone, 300 to 800 micrograms/day for at least 6 months (mean 25 months), was therefore undertaken in children. In part 1 of the study, 18 children with asthma, aged 4 to 17 years (mean 10.1 years), were compared with an age- and sex-matched group of children with asthma not treated with corticosteroids. In part 2, eight more pairs were compared. Comparisons were also made with 61 healthy children. Bone mineral density measured by radiographic absorptiometry, and bone mineral content measured by single-photon absorptiometry and by dual-energy x-ray absorptiometry, showed no significant differences. Serum levels of calcium, magnesium, zinc, total alkaline phosphatase, bone specific alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D also showed no differences. The activity of tartrate-resistant acid phosphatase, a marker of bone resorption, was significantly lower in the beclomethasone group than in both the asthma control and the normal control groups, but urine calcium excretion did not differ. Patients with asthma had lower serum osteocalcin and higher serum copper levels than control subjects without asthma, but treatment with beclomethasone did not affect these values. We conclude that inhaled beclomethasone (up to 800 micrograms/day) does not reduce bone mineralization or increase bone resorption. Effects on bone formation were difficult to assess because asthma per se caused a significant reduction in osteocalcin, a sensitive marker of bone formation.

  12. Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells.

    Science.gov (United States)

    Chan, B Y; Lau, K S; Jiang, B; Kennelly, E J; Kronenberg, F; Kung, A W C

    2008-09-01

    Aceaea racemosa (formerly Cimicifuga racemosa, black cohosh, AR) extracts have been widely used as an alternative to hormonal replacement therapy for menopausal symptoms. Recent evidences suggest AR extracts are also effective in protecting against postmenopausal bone loss. To determine whether AR has any direct anabolic effect on osteoblasts, we investigated the ethanolic extract of AR on bone nodule formation in mouse MC3T3-E1 preosteoblast cells. AR did not stimulate osteoblast proliferation. Rather, at high doses of 1000 ng/mL for 48 h, AR suppressed (7.2+/-0.9% vs. control) osteoblast proliferation. At 500 ng/mL, a significant increase in bone nodule formation was seen with Von Kossa staining. Using quantitative PCR analysis, AR was shown to enhance the gene expression of runx2 and osteocalcin. Co-treatment with ICI 182,780, the selective estrogen receptor antagonist, abolished the stimulatory effect of AR on runx2 and osteocalcin gene induction, as well as on bone nodule formation in MC3T3-E1 cells. This is a first report of the direct effect of AR on enhancement of bone nodule formation in osteoblasts, and this action was mediated via an estrogen receptor-dependent mechanism. The results provide a scientific rationale at the molecular level for the claim that AR can offer effective prevention of postmenopausal bone loss.

  13. Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats

    DEFF Research Database (Denmark)

    Zengin, Ayse; Kropp, Benedikt; Chevalier, Yan

    2016-01-01

    the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist. METHODS: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), "Atkins-style" protein-matched diet (LC-HF-1), or ketogenic......PURPOSE: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while...... low-protein diet (LC-HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography-tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay...

  14. The effects of hydroxyapatite coating and bone allograft on fixation of loaded experimental primary and revision implants

    DEFF Research Database (Denmark)

    Søballe, Kjeld; Mouzin, Olivier R G; Kidder, Louis A;

    2003-01-01

    We used our established experimental model of revision joint replacement to examine the roles of hydroxyapatite coating and bone graft in improving the fixation of revision implants. The revision protocol uses the Søballe micromotion device in a preliminary 8-week period of implant instability...... for the presence of particulate polyethylene. During this procedure, a sclerotic endosteal bone rim forms, and a dense fibrous membrane is engendered, having macrophages with ingested polyethylene and high levels of inflammatory cytokines. At the time of revision after 8 weeks, the cavity is revised with either...... in each of the 8 treatment groups (total 64 implants in 32 dogs). The observation period was 4 weeks after revision. Outcome measures are based on histomorphometry and mechanical pushout properties. The revision setting was always inferior to its primary counterpart. Bone graft improved the revision...

  15. Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

    Science.gov (United States)

    van Dussen, L; Lips, P; van Essen, H W; Hollak, C E M; Bravenboer, N

    2014-09-01

    Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

  16. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells

    Science.gov (United States)

    2016-01-01

    Background Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. Materials and Methods In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Results Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Conclusion Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft. PMID:27606597

  17. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice.

    Science.gov (United States)

    Mori-Okamoto, Junko; Otawara-Hamamoto, Yoko; Yamato, Hideyuki; Yoshimura, Hiroyuki

    2004-05-01

    Pomegranate is known to contain estrogens (estradiol, estrone, and estriol) and show estrogenic activities in mice. In this study, we investigated whether pomegranate extract is effective on experimental menopausal syndrome in ovariectomized mice. Prolongation of the immobility time in forced swimming test, an index of depression, was measured 14 days after ovariectomy. The bone mineral density (BMD) of the tibia was measured by X-ray absorptiometry and the structure and metabolism of bone were also analyzed by bone histomorphometry. Administration of pomegranate extract (juice and seed extract) for 2 weeks to ovariectomized mice prevented the loss of uterus weight and shortened the immobility time compared with 5% glucose-dosed mice (control). In addition, ovariectomy-induced decrease of BMD was normalized by administration of the pomegranate extract. The bone volume and the trabecular number were significantly increased and the trabecular separation was decreased in the pomegranate-dosed group compared with the control group. Some histological bone formation/resorption parameters were significantly increased by ovariectomy but were normalized by administration of the pomegranate extract. These changes suggest that the pomegranate extract inhibits ovariectomy-stimulated bone turnover. It is thus conceivable that pomegranate is clinically effective on a depressive state and bone loss in menopausal syndrome in women.

  18. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    Science.gov (United States)

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  19. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  20. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  1. Bone Healing Improvements Using Hyaluronic Acid and Hydroxyapatite/Beta-Tricalcium Phosphate in Combination: An Animal Study

    Science.gov (United States)

    Chang, Yen-Lan; Lo, Yi-June; Huang, Yu-Chih; Tsai, Hsin-Yuan; Lin, Che-Tong; Fan, Kan-Hsin

    2016-01-01

    The purpose of this study was to investigate whether the use of HLA as an aqueous binder of hydroxyapatite/beta-tricalcium phosphate (HA-βTCP) particles can reduce the amount of bone graft needed and increase ease of handling in clinical situations. In this study, HA/βTCP was loaded in commercially available crosslinking HLA to form a novel HLA/HA-βTCP composite. Six New Zealand White rabbits (3.0–3.6 kg) were used as test subjects. Four 6 mm defects were prepared in the parietal bone. The defects were filled with the HLA/HA-βTCP composite as well as HA-βTCP particle alone. New bone formation was analyzed by micro-CT and histomorphometry. Our results indicated that even when the HA-βTCP particle numbers were reduced, the regenerative effect on bone remained when the HLA existed. The bone volume density (BV/TV ratio) of HLA/HA-βTCP samples was 1.7 times larger than that of the control sample at week 2. The new bone increasing ratio (NBIR) of HLA/HA-βTCP samples was 1.78 times higher than the control group at week 2. In conclusion, HA-βTCP powder with HLA contributed to bone healing in rabbit calvarial bone defects. The addition of HLA to bone grafts not only promoted osteoconduction but also improved handling characteristics in clinical situations. PMID:28070520

  2. Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model.

    Science.gov (United States)

    Aro, Hannu T; Kulkova, Julia; Moritz, Niko; Kähkönen, Esa; Mattila, Riina H

    2015-01-01

    Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984). ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry. Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%). This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs.

  3. Hydroxyapatite/b-tricalcium Phosphate Composite for Guiding Bone Tissue Growth into a Titanium Tube in 8 mm Dog Tibia Cavity Defects

    Institute of Scientific and Technical Information of China (English)

    ZHU Jixiang; CHEN Xiaoming; WANG Jing; CHEN Weimin

    2016-01-01

    We developed a ifxation method and evaluate bone regrowth in the cavities of af4 mm× 8 mm titanium (Ti) tube through porous hydroxyapatite (HAP)/β-tricalcium phosphate (β-TCP) composite filling (group A), chitosan/calcium phosphate composite filling (group B), and HAP particle modification (group C). After 2 and 5 months of implantation in dog tibia defects, new bone formation in the three groups was studied by histology and histomorphometry. Group A displayed the most bone regenerated area in both 2 and 5 months post-operation. The chitosan/calcium phosphate composite in group B mostly degraded 2 months after implantation, leading to ifbrous tissue invasion after 5 months. By contrast, less bone formation was observed in group C. These results indicated that filling the cavities of metal prostheses with a porous HAP/β-TCP composite can be used for stable long-term ifxation in clinical settings.

  4. Quantification of bone mass gain in response to the application of biphasic bioceramics and platelet concentrate in critical-size bone defects.

    Science.gov (United States)

    Lobo, Sonja Ellen; Wykrota, Francisco Henrique Lanna; Oliveira, Ana Carolina Marques Barbosa; Kerkis, Irina; Mahecha, Germán Bohorquez; Alves, Humberto José

    2009-05-01

    Biphasic bioceramics have been widely indicated for bone reconstruction; however, the real gain in bone mass due to the presence of such biomaterials has not been established yet nor the advantages of its association with platelet concentrate. This study aims at quantifying the volume of bone matrix, osteoblasts, osteocytes, blood vessels and adipose tissue after the application of a biphasic bioceramics composed of 65% hydroxyapatite and 35% beta-tricalcium phosphate. Critical-size bone defects were produced in rabbit femora and reconstructed with bioceramics only, with bioceramics combined with platelet concentrate, with platelet concentrate alone, and with no treatment (blood clot). The quantitative evaluation was performed on histological sections using histomorphometry. Our data provide original evidence that consolidates the indication of bioceramics for clinical bone loss reconstruction. The application of biphasic bioceramics alone led to major bone mass gain and was followed by its association with platelet concentrate. On the other hand, platelet concentrate can contribute to the augmentation and maintenance of the adipose tissue, representing a new field for future applications in plastic surgery.

  5. Associations of total, dairy, and meat protein with markers for bone turnover in healthy, prepubertal boys

    DEFF Research Database (Denmark)

    Budek, Alicja Zofia; Hoppe, Camilla; Michaelsen, Kim Fleischer

    2007-01-01

    We previously reported that high intake of milk, but not meat, equal in protein content, increased serum insulin-like growth factor-I (sIGF-I) in prepubertal boys. sIGF-I plays a key role in bone metabolism. Therefore, the aim of this cross-sectional study was to investigate associations of total......, dairy, and meat protein intake with markers for bone turnover and sIGF-I in prepubertal, healthy boys (n ¼ 81). We measured bone turnover (enzyme-linked immunoassay) in serum osteocalcin (sOC), bone-specific alkaline phosphatase (sBAP), and C-terminal telopeptide of collagen type-I (sCTX); dietary...

  6. The influence of smoking on bone loss and response to nasal estradiol

    DEFF Research Database (Denmark)

    Bjarnason, N.H.; Nielsen, T.F.; Jørgensen, Henrik Løvendahl;

    2009-01-01

    Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc exploratory......-smokers (1.4% vs. 1.4%, p=0.89), whereas the change in the hip on the placebo was similar to that seen in the spine (-3.7% vs. -2.6%, p=0.08). Supportive changes were seen in urinary CTX and in serum osteocalcin. Conclusions These results indicate that cigarette smoking may reduce the efficacy of nasal...... estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women Udgivelsesdato: 2009...

  7. 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...

  8. Pharmacological inhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6 mice.

    Science.gov (United States)

    Duque, Gustavo; Li, Wei; Vidal, Christopher; Bermeo, Sandra; Rivas, Daniel; Henderson, Janet

    2013-03-01

    Infiltration of bone marrow with fat is a prevalent feature in people with age-related bone loss and osteoporosis, which correlates inversely with bone formation and positively with high expression levels of peroxisomal proliferator-activated receptor gamma (PPARγ). Inhibition of PPARγ thus represents a potential therapeutic approach for age-related bone loss. In this study, we examined the effect of PPARγ inhibition on bone in skeletally mature C57BL/6 male mice. Nine-month-old mice were treated with a PPARγ antagonist, bisphenol-A-diglycidyl ether (BADGE), alone or in combination with active vitamin D (1,25[OH](2) D(3) ) for 6 weeks. Micro-computed tomography and bone histomorphometry indicated that mice treated with either BADGE or BADGE + 1,25(OH)(2) D(3) had significantly increased bone volume and improved bone quality compared with vehicle-treated mice. This phenotype occurred in the absence of alterations in osteoclast number. Furthermore, the BADGE + 1,25(OH)(2) D(3) -treated mice exhibited higher levels of unmineralized osteoid. All of the treated groups showed a significant increase in circulating levels of bone formation markers without changes in bone resorption markers, while blood glucose, parathyroid hormone, and Ca(+) remained normal. Furthermore, treatment with BADGE induced higher levels of expression of vitamin D receptor within the bone marrow. Overall, treated mice showed higher levels of osteoblastogenesis and bone formation concomitant with decreased marrow adiposity and ex vivo adipogenesis. Taken together, these observations demonstrate that pharmacological inhibition of PPARγ may represent an effective anabolic therapy for osteoporosis in the near future.

  9. Effects of salvianolate on bone metabolism in glucocorticoid-treated lupus-prone B6.MRL-Faslpr/J mice

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-08-01

    Full Text Available Yanzhi Liu,1,2 Yang Cui,3 Xiao Zhang,3 Xiang Gao,4 Yanjie Su,2 Bilian Xu,2 Tie Wu,2 Wenshuang Chen,2 Liao Cui1,2 1College of Traditional Chinese Medicine, Southern Medical University, Guangzhou City, 2Department of Pharmacology, Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 3Department of Rheumatology, Guangdong Provincial People’s Hospital, Guangzhou, 4Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China Aim: To investigate the bone-protective effects of salvianolate (Sal, a total polyphenol from Radix Salviae miltiorrhizae, on bone tissue in the spontaneous lupus-prone mouse model, B6.MRL-Faslpr/J, undergoing glucocorticoid (GC treatment.Methods: Fifteen-week-old female B6.MRL-Faslpr/J mice were administered either a daily dose of saline (lupus group, prednisone 6 mg/kg (GC group, Sal 60 mg/kg (Sal group; or GC plus Sal (GC + Sal group for a duration of 12 weeks. Age-matched female C57BL/6J wild-type (WT mice were used for control. Micro-computed tomography assessments, bone histomorphometry analysis, bone biomechanical test, immunohistochemistry and immunoblotting analysis for bone markers, and renal histology analysis were performed to support our research endeavor.Results: Lupus mice developed a marked bone loss and deterioration of mechanical properties of bone due to an increase in bone resorption rather than suppression of bone formation. GC treatment strongly inhibited bone formation in lupus mice. Sal treatment significantly attenuated osteogenic inhibition, and also suppressed hyperactive bone resorption, which recovered the bone mass and mechanical properties of bone in both the untreated and GC-treated lupus mice.Conclusion: The data support further preclinical investigation of Sal as a potential therapeutic strategy for the treatment of systemic lupus erythematosus-related bone

  10. Correlating the nanoscale mechanical and chemical properties of knockout mice bones

    Science.gov (United States)

    Kavukcuoglu, Nadire Beril

    Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2

  11. Bone Mineral Density in Thalassemia Major Patients from Antalya, Turkey

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    Ibrahim Aslan

    2012-01-01

    Full Text Available Aim. We assessed the bone mineral density and related parameters in nine adults, thirty-eight pubertal, prepubertal totally forty-seven patients with thalassemia major living in Antalya, Turkey. Materials and Methods. We measured height and pubertal staging in last five years by six-month intervals. Average ferritin and hemoglobin concentrations were calculated for last three years. The levels of hydroxyproline, calcium, phosphorus, and creatinine were measured in 24 h urine, and those of parathormone, IGF 1, osteocalcine, alkaline phosphatase, calcium, ionized calcium, magnesium, phosphorus, creatine, blood glucose, thyroid stimulating hormone, alanine transaminase, and aspartate transaminase were determined in serum, and also the bone mineral density was measured. Results. The average L1–L4 bone mass density was 27.1±10.1 g cm−2; the average bone mineral content was 0.65 ± 0.11 g. of the patients with a Z-score under 2.5. A moderate relationship was found between the bone mass density age and height. Subjects in low pubertal staging and short stature (<3% percentile have significantly lower bone mass densities P<0.001. Conclusion. he prevalence of osteoporosis is high in patients with thalassemia major, possibly related to delayed puberty.

  12. Effect of the “protein diet” and bone tissue.

    Science.gov (United States)

    Nascimento da Silva, Zoraide; Azevedo de Jesuz, Vanessa; De Salvo Castro, Eduardo; Soares da Costa, Carlos Alberto; Teles Boaventura, Gilson; Blondet de Azeredo, Vilma

    2014-01-01

    The aim of this study is to evaluate the effect of the hyperproteic diet consumption on bone tissue. The study was conducted during sixty days. Twenty eight Wistar albinus rats, adults, originated from Laboratory of Experimental Nutrition were divided in four groups: (n = 7); Control 1 (C1), Control 2 (C2), Hyperproteic 1 (HP1) e Hyperproteic 2 (HP2). The C2 and HP2 groups were submitted to 30% of food restriction. The hyperproteic diet was based on the Atkins diet and prepared to simulate the protein diet. At the end of the study the animals were anesthetized to performer bone densitometry analyses by DEXA and blood and tissue collection. Serum and bone minerals analyses were conducted by colorimetric methods in automated equipment. The total bone mineral density (BMD) of the pelvis and the spine of the food restriction groups (HP2 e C2) were lower (p hyperproteic groups (HP1 e HP2). It was observed similar effect on the osteocalcin level, that presented lower (p hyperproteic groups. The insulin level was lower only in HP2 and serum calcium of the HP1 and HP2 groups was lower than C1. The protein diet promotes significant bone change on femur and in the hormones levels related to bone synthesis and maintenance of this tissue.

  13. Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China); Wang, Zhenming; Lu, Xiong [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan (China); Yimin [Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo (Japan); Oda, Kimimitsu [Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Amizuka, Norio [Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo (Japan); Li, Minqi, E-mail: liminqi@sdu.edu.cn [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China)

    2015-04-01

    The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8 weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. - Highlights: • More information on collagen material was added in the revised manuscript. • Masson–Goldner trichrome stain was performed for histomorphometry. • More specific information on calcitriol was supplemented in the Discussion section. • The MOD of ALP and Runx2 was explained in more detail. • The inhibition of osteoclastogenesis was described more accurately in the second paragraph of the discussion.

  14. Effect of dietary calcium: Phosphorus ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats.

    Science.gov (United States)

    Koshihara, Moyuru; Masuyama, Ritsuko; Uehara, Mariko; Suzuki, Kazuharu

    2004-01-01

    We investigated the effect of dietary calcium:phosphorus (Ca:P) ratio on bone mineralization and intestinal Ca absorption in ovariectomized (OVX) rat models of osteoporosis and sham-operated rats. Thirty 12-wk-old female Wistar rats were divided into three groups of OVX rats and three groups of sham rats. Thirty days after the adaptation period, OVX rats and sham rats were fed a diet formulated Ca:P, 1:0.5, 1:1 or 1:2 (each diet containing 0.5% Ca), respectively for 42 d. In both sham and OVX rats, serum osteocalcin, a marker of bone turnover, was increased by decreasing Ca:P ratio (1:2). In contrast, rats fed the Ca:P = 1:0.5 diet (dietary P restriction) suppressed the increased serum parathyroid hormone, osteocalcin and urinary deoxypyridinoline, and increased Ca absorption in both sham and OVX rats compared to the Ca:P = 1:1 and 1:2 diets. Especially, in OVX rats, the decreased bone mineral density of the fifth lumbar was also suppressed when rats were fed the Ca:P = 1:0.5 diet. These results indicated that the elevation of dietary Ca:P ratio may inhibit bone loss and increase intestinal Ca absorption in OVX rats.

  15. Agave fructans: their effect on mineral absorption and bone mineral content.

    Science.gov (United States)

    García-Vieyra, María Isabel; Del Real, Alicia; López, Mercedes G

    2014-11-01

    In this study we investigate the effect that Agave fructans as new prebiotics have on mineral absorption improvement. Forty-eight 12-week-old C57BL/6J mice were used in this study. Forty mice were ovariectomized and eight were sham-operated controls. Mice were fed standard diets or diets supplemented with 10% Agave fructans or 10% inulin fructans. Calcium and magnesium were evaluated as well as their excretion in feces. Osteocalcin levels were also measured; femur structure was studied by scanning electron microscopy. Other parameters, such as food intake, body weight, glucose, and short-chain fatty acid content, were recorded. Calcium in plasma and bone increased in Agave fructan groups (from 53.1 to 56 and 85 mg/L and from 0.402 to 0.474 and 0.478 g/g, respectively) and osteocalcin increased in all fructan groups (>50%). Scanning electron microscopy showed that fructans were able to mitigate bone loss. In conclusion, we demonstrated that supplementation with Agave fructans prevents bone loss and improves bone formation.

  16. Protection by salidroside against bone loss via inhibition of oxidative stress and bone-resorbing mediators.

    Directory of Open Access Journals (Sweden)

    Jin-Kang Zhang

    Full Text Available Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H(2O(2 in MC3T3-E1 cells and a murine ovariectomized (OVX osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0.05 elevation of cell survival, alkaline phosphatase (ALP staining and activity, calcium deposition, and the transcriptional expression of Alp, Col1a1 and Osteocalcin (Ocn in the presence of H(2O(2. Moreover, salidroside decreased the production of intracellular reactive oxygen species (ROS, and osteoclast differentiation inducing factors such as receptor activator of nuclear factor-kB ligand (RANKL and IL-6 induced by H(2O(2. In vivo studies further demonstrated that salidroside supplementation for 3 months caused a decrease in malondialdehyde (MDA and an increase in reduced glutathione (GSH concentration in blood of ovariectomized mouse (P<0.05, it also improved trabecular bone microarchitecture and bone mineral density in the fourth lumbar vertebra and distal femur. Our study indicated that the protection provided by salidroside in alleviating bone loss was mediated, at least in part, via inhibition of the release of bone-resorbing mediators and oxidative damage to bone-forming cells, suggesting that salidroside can be used as an effective remedy in the treatment or prevention of osteoporosis.

  17. Effect of tetracalcium dimagnesium phytate on bone characteristics in ovariectomized rats.

    Science.gov (United States)

    Grases, Félix; Sanchis, Pilar; Prieto, Rafael M; Perelló, Joan; López-González, Ángel A

    2010-12-01

    The aim was to evaluate the influence of dietary Ca-Mg-phytate consumption on the bone characteristics of ovariectomized rats, an animal model for postmenopausal osteoporosis. Twenty ovariectomized female Wistar rats were randomly assigned to two groups fed, respectively, with a non-phytate diet (AIN-76A) or the same diet enriched with 1% phytate (as the calcium magnesium salt, phytin). After 12 weeks of feeding the rats were sacrificed, and both femoral bones and L4 vertebra were removed from each rat. Bone mass, length, width, volume, and mineral density were measured, and the phosphorus, calcium, magnesium, and zinc contents of bones were determined. Deoxypyridinoline (a bone resorption marker) was measured in urine, and osteocalcin (a bone formation marker) was measured in serum. The calcium and phosphorus contents and bone mineral density were significantly higher in both femoral bones and L4 vertebra for phytate-treated rats in comparison to rats in the non-phytate group. Deoxypyridinoline was significantly increased in rats in the non-phytate treatment group. Ca-Mg-phytate consumption reduces bone mineral density loss due to estrogen deficiency. Thus, phytate exhibits effects similar to those of bisphosphonates on bone resorption and may be of use in the primary prevention of osteoporosis if larger studies in humans confirm these findings.

  18. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    Science.gov (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  19. Bone: a new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders.

    Science.gov (United States)

    Vervloet, Marc G; Massy, Ziad A; Brandenburg, Vincent M; Mazzaferro, Sandro; Cozzolino, Mario; Ureña-Torres, Pablo; Bover, Jordi; Goldsmith, David

    2014-05-01

    Recent reports of several bone-derived substances, some of which have hormonal properties, have shed new light on the bone-cardiovascular axis. Deranged concentrations of humoral factors are not only epidemiologically connected to cardiovascular morbidity and mortality, but can also be causally implicated, especially in chronic kidney disease. FGF23 rises exponentially with advancing chronic kidney disease, seems to reach maladaptive concentrations, and then induces left ventricular hypertrophy, and is possibly implicated in the process of vessel calcification. Sclerostin and DKK1, both secreted mainly by osteocytes, are important Wnt inhibitors and as such can interfere with systems for biological signalling that operate in the vessel wall. Osteocalcin, produced by osteoblasts or released from mineralised bone, interferes with insulin concentrations and sensitivity, and its metabolism is disturbed in kidney disease. These bone-derived humoral factors might place the bone at the centre of cardiovascular disease associated with chronic kidney disease. Most importantly, factors that dictate the regulation of these substances in bone and subsequent secretion into the circulation have not been researched, and could provide entirely new avenues for therapeutic intervention.

  20. Effects of high-fat diet on bone strength and metabolic indices of ovariectomized rats%高脂饮食对去卵巢大鼠骨强度及骨代谢的影响

    Institute of Scientific and Technical Information of China (English)

    朱小欢; 尹倩倩; 鲍莹莹; 代芳; 张楠; 鲁云霞; 章秋

    2016-01-01

    Objective To observe the effects of high-fat diet on bone strength and metabolic indices of ovariecto-mized rats. Methods Female SD rats were randomly divided into sham operated group fed normal chow( SHAM) , sham operated group fed high-fat diet ( HFD ) , ovariectomized group fed normal chow ( OVX ) and ovariectomized group treated with high-fat diet ( OVX-HFD ) . The HFD and OVX-HFD group were fed high-fat diet containing 30% fat for 28 weeks. At the end of the experiment, serum N-MID osteocalcin( N-MID-OT) and tartrate-resistant acid phosphatase(TRAP) were detected; the bone mineral density(BMD) and bone mineral content(BMC) of rats′right femurs and lumbar vertebras, the biomechanics of rats′left femurs and contents of hydroxyproline, calci-um and phosphorus of rats′left femurs were determined. HE staining was used to observe the morphology of rat tra-becula in the distal femoral metaphysis and the static parameters of distal femoral cancellous bone histomorphometry were calculated. Results Compared with SHAM group, serum TRAP level and femoral trabecular bone separation were significantly increased(P=0. 000,0. 035), while femoral BMD,BMC,elastic load, maximum load and con-tents of hydroxyproline and calcium were decreased remarkably(P<0. 05,P<0. 01)in OVX group. Compared with those in SHAM group, the serum levels of N-MID-OT and TRAP were elevated significantly(P=0. 007,0. 000), and the BMD, BMC of femurs and lumbar vertebras, elastic load, maximum load, femoral calcium contents, the percentage of femoral trabecular bone area and trabecular bone thickness were increased ( P <0. 05 , P <0. 01 ) in HFD group. Compared with OVX group, the BMD,BMC of femursand lumbar vertebras, elastic load, maximum load,femoral calcium contents,the percentage of femoral trabecular bone area and trabecular bone thickness were significantly increased(P<0. 05,P<0. 01), while serum levels of N-MID-OT and TRAP were increased without obvious differences in OVX-HFD group

  1. Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

    Science.gov (United States)

    Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

    2014-10-01

    Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (pBone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (pbone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

  2. The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism

    Directory of Open Access Journals (Sweden)

    J. Kelly Smith

    2016-01-01

    Full Text Available Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α, antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10, pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6, and T cell growth and differentiation factors (interleukins 2 and 12 by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin, bone resorption (C-terminal telopeptides of Type I collagen, and bone homeostasis (25 (OH vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1. A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Trials.gov Identifier: NCT02765945.

  3. Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Jackson, M A; Iwaniec, U T; Turner, R T; Wronski, T J; Kalra, S P

    2011-08-01

    Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. 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.

  5. Mechanical stress induces bone formation in the maxillary sinus in a short-term mouse model.

    Science.gov (United States)

    Kuroda, Shingo; Wazen, Rima; Moffatt, Pierre; Tanaka, Eiji; Nanci, Antonio

    2013-01-01

    Clinicians occasionally face the challenge of moving a tooth through the maxillary sinus. The objective of this study was to evaluate tissue remodeling during tooth movement into the maxillary sinus, more specifically as regards to bone formation. The maxillary first molar of 20 male mice was moved toward the palatal side by a nickel-titanium super elastic wire for 1 to 14 days, and the bone remodeling around the root was evaluated using histomorphometry and immunodetection of bone-restricted Ifitm-like (Bril) protein, a novel marker of active bone formation. When mechanical stress was applied to the tooth, the periodontal ligament on the palatal side was immediately compressed to approximately half of its original width by the tipping movement of the tooth. At the same time, osteoblasts deposited new bone on the wall of the maxillary sinus prior to bone resorption by osteoclasts on the periodontal side, as evidenced by the high level of expression of Bril at this site. As a result of these sequential processes, bone on the sinus side maintained a consistent thickness during the entire observation period. No root resorption was observed. Bone formation on the surface of the maxillary sinus was evoked by mechanotransduction of mechanical stress applied to a tooth over a 2-week period, and was induced ahead of bone resorption on the periodontal ligament side. Mechanical stress can be exploited to induce bone formation in the maxillary sinus so that teeth can be moved into the sinus without losing bone or causing root damage.

  6. Muscle and bone, two interconnected tissues.

    Science.gov (United States)

    Tagliaferri, Camille; Wittrant, Yohann; Davicco, Marie-Jeanne; Walrand, Stéphane; Coxam, Véronique

    2015-05-01

    As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Craniofacial vertical bone augmentation: a comparison between 3D printed monolithic monetite blocks and autologous onlay grafts in the rabbit.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesus; Gbureck, Uwe; Lopez-Cabarcos, Enrique; Bassett, David C; Alkhraisat, Mohammad H; Barralet, Jake E

    2009-10-01

    Onlay autografting is amongst the most predictable techniques for craniofacial vertical bone augmentation, however, complications related to donor site surgery are common and synthetic alternatives to onlay autografts are desirable. Recent studies have shown that the acidic calcium phosphates, brushite and monetite, are osteoconductive, osteoinductive and resorb faster in vivo than hydroxyapatite. Moreover, they can be 3D printed allowing precise host bone-implant conformation. The objectives of this study were to confirm that craniofacial screw fixation of 3D printed monetite blocks was possible and to compare the resulting vertical bone augmentation with autograft. 3D printed monolithic monetite onlay implants were fixed with osteosynthesis screws on the calvarial bone surface of New Zealand rabbits. After 8 weeks, integration between the implant and the calvarial bone surface was observed in all cases. Histomorphometry revealed that 42% of the monetite was resorbed and that the new bone formed within the implant occupied 43% of its volume, sufficient for immediate dental implant placement. Bone tissue within the autologous onlay occupied 60% of the volume. We observed that patterns of regeneration within the implants differed throughout the material and propose that this was due to the anatomy and blood supply pattern in the region. Rapid prototyped monetite being resorbable osteoconductive and osteoinductive would appear to be a promising biomaterial for many bone regeneration strategies.

  8. Wavelet based characterization of ex vivo vertebral trabecular bone structure with 3T MRI compared to microCT

    Energy Technology Data Exchange (ETDEWEB)

    Krug, R; Carballido-Gamio, J; Burghardt, A; Haase, S; Sedat, J W; Moss, W C; Majumdar, S

    2005-04-11

    Trabecular bone structure and bone density contribute to the strength of bone and are important in the study of osteoporosis. Wavelets are a powerful tool to characterize and quantify texture in an image. In this study the thickness of trabecular bone was analyzed in 8 cylindrical cores of the vertebral spine. Images were obtained from 3 Tesla (T) magnetic resonance imaging (MRI) and micro-computed tomography ({micro}CT). Results from the wavelet based analysis of trabecular bone were compared with standard two-dimensional structural parameters (analogous to bone histomorphometry) obtained using mean intercept length (MR images) and direct 3D distance transformation methods ({micro}CT images). Additionally, the bone volume fraction was determined from MR images. We conclude that the wavelet based analyses delivers comparable results to the established MR histomorphometric measurements. The average deviation in trabecular thickness was less than one pixel size between the wavelet and the standard approach for both MR and {micro}CT analysis. Since the wavelet based method is less sensitive to image noise, we see an advantage of wavelet analysis of trabecular bone for MR imaging when going to higher resolution.

  9. Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells.

    Science.gov (United States)

    Bockman, R S; Guidon, P T; Pan, L C; Salvatori, R; Kawaguchi, A

    1993-08-01

    Gallium is a Group IIIa transitional element with therapeutic efficacy in the treatment of metabolic bone disorders. Previously described antiresorptive effects of gallium on osteoclasts are not sufficient to account for the full range of effects of gallium on bone structure and metabolism. We have recently shown that gallium nitrate inhibits osteocalcin gene expression and the synthesis of osteocalcin protein, an osteoblast-specific bone matrix protein that is thought to serve as a signal to trigger osteoclastic resorption. Here we present evidence for an additional mechanism by which gallium may function to augment bone mass by altering matrix protein synthesis by osteoblastic and fibroblastic cells. Rat calvarial explants exposed to gallium nitrate for 48 h showed increased incorporation of 3H-proline into hydroxyproline and collagenase digestible protein. In addition, gallium treatment increased steady-state mRNA levels for fibronectin and type I procollagen chains in primary rat calvarial osteoblast-enriched cultures, the ROS 17/2.8 osteoblastic osteosarcoma line, and nontransformed human dermal fibroblasts. These findings suggest that the exposure of mesenchymally-derived cells to gallium results in an altered pattern of matrix protein synthesis that would favor increased bone formation.

  10. The spectrum of bone disease in end-stage renal failure--an evolving disorder.

    Science.gov (United States)

    Sherrard, D J; Hercz, G; Pei, Y; Maloney, N A; Greenwood, C; Manuel, A; Saiphoo, C; Fenton, S S; Segre, G V

    1993-02-01

    We have assessed the bone histology in 259 chronic dialysis patients, all of whom were in the same dialysis program. All patients had bone biopsies with quantitative histomorphometry, intact parathyroid hormone (PTH) measurements, basal and deferoxamine stimulated serum aluminum levels. Results demonstrate the increased incidence of the recently described aplastic bone lesion, particularly in patients treated with peritoneal dialysis (PD). Aluminum-related bone disease is much less common than previously described, perhaps in relation to the declining use of aluminum as a phosphate binder. A different pattern of bone lesions is seen in PD as compared with hemodialysis (HD), with low turnover disorders comprising 66% of the lesions seen in PD and high turnover lesions accounting for 62% of the bone histologic findings in HD. The difference in these patterns may relate to alterations in PTH levels, as mean PTH levels in HD patients were 2-1/2 times the levels found in PD patients (P < 0.0005), while older age, higher prevalence of diabetes and a shorter duration of dialysis may also have contributed to the findings in the PD patients. We suggest that PD, perhaps by maintaining calcium at higher levels, may more effectively suppress the parathyroid gland.

  11. Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures

    Directory of Open Access Journals (Sweden)

    Cristina de Mello-Sampayo

    2017-01-01

    Full Text Available There is controversy concerning the diabetes impact on bone quality, notorious in type 2 diabetic postmenopausal women. One pointed cause might be uncontrolled glycemia. In this study, the effect of chronic hyperglycemia in bone turnover, morphology, and biomechanics was evaluated in female Wistar rats in the presence/absence of estrogens (ovariectomy. Animals (n=28 were divided into sham, ovariectomized (OVX, hyperglycemic (streptozotocin 40 mg/kg, single-dose i.p.-STZ, and hyperglycemic-ovariectomized (STZ + OVX animals. Blood biomarkers were estimated 60 days postovariectomy. Body weight, vertebral microarchitecture (L4-histomorphometry, femur biomechanical properties (bending tests, tibia ultrastructure (scannin