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Sample records for bone growth mechanical

  1. Bone Growth, Mechanical Stimulus and IGF-1

    National Research Council Canada - National Science Library

    Gilsanz, Vicente

    2006-01-01

    ... in the weight bearing skeleton of young adult females with low bone density. Ultimately, this information could be of great benefit to enhance musculoskeletal development and decrease the risk for stress fractures in military recruits...

  2. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    OpenAIRE

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

  3. Bone Growth Mechanical Stimulus and IGF-I

    National Research Council Canada - National Science Library

    Gilsanz, Vicente

    2003-01-01

    .... This study also examines the possible relations between the cross-sectional properties of bone and circulating levels of IGF-I, IGF-binding protein-3, and IGF-I genotypes in teenagers ages 15 to 20...

  4. Bone Growth, Mechanical Stimulus and IGF-I

    National Research Council Canada - National Science Library

    Gilsanz, Vicente

    2002-01-01

    ... exercise intervention or no intervention. This study also examines the possible relations between the cross-sectional properties of bone and circulating levels of IGF-I, JGF-binding protein-3, and IGF-I genotypes in teenagers...

  5. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Erika Kristensen

    2012-01-01

    Full Text Available Growth hormone (GH deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD mouse model undergoing GH treatment commencing at an early (prepubertal or late (postpubertal time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS controls (P<0.001. GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV and trabecular thickness (Tb.Th, respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp. than the GHS controls (P<0.001. Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls and the whole bone mechanical properties (24 to 43% larger than GHD animals although there remained a sustained 27–52% net deficit compared to normal mice (P<0.05. Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD.

  6. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

    Science.gov (United States)

    Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2015-04-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

  7. Effect of dietary boron on growth performance, calcium and phosphorus metabolism, and bone mechanical properties in growing barrows.

    Science.gov (United States)

    Armstrong, T A; Spears, J W

    2001-12-01

    An experiment was conducted to evaluate the effects of dietary boron (B) on growth performance, bone mechanical properties, and calcium (Ca) and phosphorus (P) metabolism in pigs. Thirty-six barrows were weaned at approximately 21 d of age and randomly assigned to receive one of three dietary treatments. Treatments consisted of 1) low-B basal diet (control), 2) basal + 5 mg B/kg diet, and 3) basal + 15 mg B/kg diet. Boron was supplemented as sodium borate. Barrows remained on their respective experimental diets throughout the nursery (35 d) and growing (30 d) phases of production. Blood samples were obtained from each barrow at the end of each phase. Following the 30-d growing period, eight barrows per treatment were transferred to stainless steel metabolism crates. Barrows had an adjustment period of 7 d, followed by a 7-d total collection of urine and feces. All barrows were fed at 90% of the previous ad libitum grower intake of the control animals during the adjustment and collection periods. At the end of the 7-d collection period, barrows were killed and femurs and fibulas were harvested for the assessment of bone mechanical properties. During the nursery phase, ADG and ADFI were increased (P 0.05) by dietary B. These data indicate that B supplementation to pigs can increase growth and bone strength without greatly affecting Ca and P metabolism.

  8. Growth hormone and bone health.

    Science.gov (United States)

    Bex, Marie; Bouillon, Roger

    2003-01-01

    Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

  9. Mechanical property, degradation rate, and bone cell growth of chitosan coated titanium influenced by degree of deacetylation of chitosan.

    Science.gov (United States)

    Yuan, Youling; Chesnutt, Betsy M; Wright, Lee; Haggard, Warren O; Bumgardner, Joel D

    2008-07-01

    Chitosan has shown promise as a coating for dental/craniofacial and orthopaedic implants. However, the effects of degree of deacetylation (DDA) of chitosan on coating bond strength, degradation, and biological performance is not known. The aim of this project was to evaluate bonding, degradation, and bone cell growth on titanium coated with chitosans of different DDA and from different manufacturers. Three different chitosans, 80.6%, 81.7%, and 92.3% DDA were covalently bonded to titanium coupons via silane-glutaraldehyde molecules. Bond strengths were evaluated in mechanical tensile tests, and degradation, over 5 weeks, was conducted in cell culture medium with and without 100 microg/mL lysozyme. Cytocompatibility was evaluated for 10 days using UMR 106 osteoblastic cells. Results showed that mean chitosan coating bond strengths ranged from 2.2-3.8 MPa, and that there was minimal affect of DDA on coating bond strengths. The coatings exhibited little dissolution over 5 weeks in medium with or without lysozyme. However, the molecular weight (MW) of the chitosan coatings remaining on the titanium samples after 5 weeks decreased by 69-85% with the higher DDA chitosan coatings exhibiting less percent change in MW than the lower DDA materials. The growth of the UMR 106 osteoblast cells on the 81.7% DDA chitosan coating was lower on days 3 and 5, as compared with the other two coatings, but by day 10, there were no differences in growth among three coatings or to the uncoated titanium controls. Differences in growth were attributed to differences in manufacturer source material, though all coatings were judged to be osteocompatible in vitro. 2007 Wiley Periodicals, Inc.

  10. Disturbances of bone growth and development

    International Nuclear Information System (INIS)

    Ledesma-Medina, J.; Newman, B.; Oh, K.S.

    1988-01-01

    ''What is growth anyway? Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age? Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but the early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability. 116 references

  11. Mechanism of cancer-induced bone destruction: An association of connective tissue growth factor (CTGF/CCN2 in the bone metastasis

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Shimo

    2011-02-01

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family, a novel class of extracellular signal modulators. CCN2 is composed of four conserved modules connected in tandem, each of which is rich in cysteines and highly interactive with other molecules. CCN2 has various biological functions, being active in developmental processes including angiogenesis, chondrogenesis, and osteogenesis. Recently CCN2 has gained more clinical interest due to its role in cancer-induced bone destruction. In this article, the role of CCN2 in bone-destroying events as an organizer of the microenvironmental cell society is comprehensively described, and a brief summary of the recent findings on regulatory factors involved in tumor-induced bone disease is given.

  12. Biomimetic growth and substrate dependent mechanical properties of bone like apatite nucleated on Ti and magnetron sputtered TiO2 nanostructure

    Science.gov (United States)

    Sarma, Bimal K.; Das, Apurba; Barman, Pintu; Pal, Arup R.

    2016-04-01

    This report presents findings on biomimetic growth of hydroxyapatite (HAp) nanocrystals on Ti and sputtered TiO2 substrates. The possibility of TiO2 nanostructure as candidate materials for future biomedical applications has been explored through the comparison of microstructural and mechanical properties of bone like apatite grown on Ti and nano-TiO2 surfaces. Raman spectroscopy and x-ray diffraction studies reveal formation of carbonate apatite with apparent domain size in the nanoscale range. A better interaction at the nano-TiO2/nano-HAp interface due to higher interfacial area could promote the growth of bone like apatite. The crystal phases, crystallinity, and surface morphology of nano-TiO2 are considered as parameters to understand the nucleation and growth of apatite with different mechanical properties at the nanoscale. The methodology of x-ray line profile analysis encompasses deconvolution of merged peaks by preserving broadening due to nanosized HAp aggregates. The Young’s modulus of bone like apatite exhibits crystallographic directional dependence which suggests the presence of elastic anisotropy in bone like apatite. The lattice contraction in the c-direction is associated with the degree of carbonate substitution in the apatite lattice. The role of residual stress is critical for the lattice distortion of HAp deposited at physiological conditions of temperature and pH of human blood plasma. The ion concentration is crucial for the uniformity, crystallinity, and mechanical behaviour of the apatite.

  13. Biomimetic growth and substrate dependent mechanical properties of bone like apatite nucleated on Ti and magnetron sputtered TiO2 nanostructure

    International Nuclear Information System (INIS)

    Sarma, Bimal K; Das, Apurba; Barman, Pintu; Pal, Arup R

    2016-01-01

    This report presents findings on biomimetic growth of hydroxyapatite (HAp) nanocrystals on Ti and sputtered TiO 2 substrates. The possibility of TiO 2 nanostructure as candidate materials for future biomedical applications has been explored through the comparison of microstructural and mechanical properties of bone like apatite grown on Ti and nano-TiO 2 surfaces. Raman spectroscopy and x-ray diffraction studies reveal formation of carbonate apatite with apparent domain size in the nanoscale range. A better interaction at the nano-TiO 2 /nano-HAp interface due to higher interfacial area could promote the growth of bone like apatite. The crystal phases, crystallinity, and surface morphology of nano-TiO 2 are considered as parameters to understand the nucleation and growth of apatite with different mechanical properties at the nanoscale. The methodology of x-ray line profile analysis encompasses deconvolution of merged peaks by preserving broadening due to nanosized HAp aggregates. The Young’s modulus of bone like apatite exhibits crystallographic directional dependence which suggests the presence of elastic anisotropy in bone like apatite. The lattice contraction in the c-direction is associated with the degree of carbonate substitution in the apatite lattice. The role of residual stress is critical for the lattice distortion of HAp deposited at physiological conditions of temperature and pH of human blood plasma. The ion concentration is crucial for the uniformity, crystallinity, and mechanical behaviour of the apatite. (paper)

  14. The cell biology of bone growth.

    Science.gov (United States)

    Price, J S; Oyajobi, B O; Russell, R G

    1994-02-01

    The field of bone cell biology is clearly of relevance to the problem of stunting in children, as in the final analysis the cells of the growing long bone are the ultimate 'regulators'. It is the alterations in the functions of these cells that manifests as a reduction in height. Normal longitudinal growth is achieved by the coordinated recruitment, proliferation, differentiation, maturation and eventual death of the cells of growth plate and bone. Cellular activity is closely regulated by endocrine factors acting directly or indirectly, with factors produced locally and stored within the bone and cartilage microenvironment having a critical role in intercellular communication. Disruption of any of these processes can lead to growth disturbances, since it only requires a defect in a single gene to have profound effects. Studies in recent years have shed light on the biochemical and molecular effects of cytokines and growth factors and have shown that these regulatory molecules may mediate the effects of certain hormones important in controlling growth. However, the complex interrelationship of these molecules is still not clear. Notwithstanding, understanding of the mechanisms involved in bone remodelling is increasing, as this area attracts much research because of the high incidence of metabolic bone disease in Western society. Although studies of adult bone remodelling are of relevance, there is a requirement for increased research directed specifically at the mechanisms of endochondral ossification and its regulation. Longitudinal bone growth is a challenge to the cell biologist, since it is an accelerated cycle of cellular division and differentiation, within which it is not easy to separate events temporally and spatially. In addition, different regulatory mechanisms are probably important at different stages of growth. Another difficulty impeding progress in this field is the lack of appropriate animal models for research. Much information has come from

  15. Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

    Science.gov (United States)

    Linderman, Jon K.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Grindeland, Richard E.

    1994-01-01

    growth of hindlimb bones in the absence of mechanical load.

  16. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  17. Molecular mechanism and potential targets for bone metastasis

    International Nuclear Information System (INIS)

    Iguchi, Haruo

    2007-01-01

    The incidence of bone metastasis has been increasing in all cancers in recent years. Bone metastasis is associated with substantial morbidity, including bone pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the management of bone metastasis in patients is a clinically significant issue. In the process of bone metastasis, the primary mechanism responsible for bone destruction is cancer cell-mediated stimulation of osteoclastic bone resorption, which results in osteolysis and release of various growth factors from the bone matrix. These growth factors are prerequisites for successful colonization and subsequent invasive growth of cancer cells in bone, which is called a 'vicious cycle.' Thus, it is important to elucidate what molecules are involved in this step of bone destruction, and the understanding of these molecular mechanisms could lead to develop molecular-target therapies for bone metastasis. Bisphosphonates introduced in the treatment for bone metastasis have been shown to reduce skeletal morbidity. In Japan, the most potent bisphosphonate, zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical trial of humanized anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Denosumab) against bone metastasis is under way as a global study. These new agents, which are targeted to osteoclasts, are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and/or hormone therapy. (author)

  18. Effects of Testosterone and Growth Hormone on the Structural and Mechanical Properties of Bone by Micro-MRI in the Distal Tibia of Men With Hypopituitarism

    Science.gov (United States)

    Al Mukaddam, Mona; Rajapakse, Chamith S.; Bhagat, Yusuf A.; Wehrli, Felix W.; Guo, Wensheng; Peachey, Helen; LeBeau, Shane O.; Zemel, Babette S.; Wang, Christina; Swerdloff, Ronald S.; Kapoor, Shiv C.

    2014-01-01

    Context: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD. Objective: Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism. Design and Subjects: This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism. Intervention: Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years. Main Outcome Measures: We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment. Results: Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone. PMID:24423356

  19. Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism.

    Science.gov (United States)

    Al Mukaddam, Mona; Rajapakse, Chamith S; Bhagat, Yusuf A; Wehrli, Felix W; Guo, Wensheng; Peachey, Helen; LeBeau, Shane O; Zemel, Babette S; Wang, Christina; Swerdloff, Ronald S; Kapoor, Shiv C; Snyder, Peter J

    2014-04-01

    Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD. Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism. This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism. Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years. We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment. Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.

  20. 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

    Science.gov (United States)

    Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

    2017-09-01

    In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

  1. Mechanisms of growth plate maturation and epiphyseal fusion

    NARCIS (Netherlands)

    Emons, J.; Chagin, A.S.; Karperien, Hermanus Bernardus Johannes; Wit, J.M.

    2011-01-01

    Longitudinal growth occurs within the long bones at the growth plate. During childhood, the growth plate matures, its total width decreases and eventually it disappears at the end of puberty with complete replacement by bone along with cessation of longitudinal growth. The exact mechanism of

  2. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. © 2016 Wiley Periodicals, Inc.

  3. Molecular Mechanisms That Contribute to Bone Marrow Pain

    Directory of Open Access Journals (Sweden)

    Jason J. Ivanusic

    2017-09-01

    Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

  4. Effects of Growth Hormone on Bone.

    Science.gov (United States)

    Tritos, Nicholas A; Klibanski, Anne

    2016-01-01

    Describe the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on the skeleton. The GH and IGF-1 axis has pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. GH deficiency leads to decreased bone turnover, delayed statural growth in children, low bone mass, and increased fracture risk in adults. GH replacement improves adult stature in GH deficient children, increases bone mineral density (BMD) in adults, and helps to optimize peak bone acquisition in patients, during the transition from adolescence to adulthood, who have persistent GH deficiency. Observational studies suggest that GH replacement may mitigate the excessive fracture risk associated with GH deficiency. Acromegaly, a state of GH and IGF-1 excess, is associated with increased bone turnover and decreased BMD in the lumbar spine observed in some studies, particularly in patients with hypogonadism. In addition, patients with acromegaly appear to be at an increased risk of morphometric-vertebral fractures, especially in the presence of active disease or concurrent hypogonadism. GH therapy also has beneficial effects on statural growth in several conditions characterized by GH insensitivity, including chronic renal failure, Turner syndrome, Prader-Willi syndrome, postnatal growth delay in patients with intrauterine growth retardation who do not demonstrate catchup growth, idiopathic short stature, short stature homeobox-containing (SHOX) gene mutations, and Noonan syndrome. GH and IGF-1 have important roles in skeletal physiology, and GH has an important therapeutic role in both GH deficiency and insensitivity states. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Toward mechanical systems biology in bone.

    Science.gov (United States)

    Trüssel, Andreas; Müller, Ralph; Webster, Duncan

    2012-11-01

    Cyclic mechanical loading is perhaps the most important physiological factor regulating bone mass and shape in a way which balances optimal strength with minimal weight. This bone adaptation process spans multiple length and time scales. Forces resulting from physiological exercise at the organ scale are sensed at the cellular scale by osteocytes, which reside inside the bone matrix. Via biochemical pathways, osteocytes orchestrate the local remodeling action of osteoblasts (bone formation) and osteoclasts (bone resorption). Together these local adaptive remodeling activities sum up to strengthen bone globally at the organ scale. To resolve the underlying mechanisms it is required to identify and quantify both cause and effect across the different scales. Progress has been made at the different scales experimentally. Computational models of bone adaptation have been developed to piece together various experimental observations at the different scales into coherent and plausible mechanisms. However additional quantitative experimental validation is still required to build upon the insights which have already been achieved. In this review we discuss emerging as well as state of the art experimental and computational techniques and how they might be used in a mechanical systems biology approach to further our understanding of the mechanisms governing load induced bone adaptation, i.e., ways are outlined in which experimental and computational approaches could be coupled, in a quantitative manner to create more reliable multiscale models of bone.

  6. The fracture properties and toughening mechanisms of bone and dentin

    Science.gov (United States)

    Koester, Kurt John

    The mechanical properties of bone and dentin and in particular their fracture properties, are the subject of intense research. The relevance of these properties is increasing as our population ages and fracture incidence impacts the lives of a greater portion of the population. A robust framework is needed to understand the fracture properties of bone and dentin to guide researchers as they attempt to characterize the effects of aging, disease, and pharmaceutical treatments on the properties of these mineralized tissues. In the present work, this framework is provided and applied to human bone, human dentin, and animal bone. In situ electron microscopy was also used to identify the salient toughening mechanisms in bone and dentin. It was found that bone and dentin are extrinsically toughened materials and consequently their fracture properties are best characterized utilizing a crack-growth resistance approach. A description of the different mechanical measurements commonly employed when using small animal models (rats and mice) to evaluate the influence of drug therapies on bone fragility is provided. A study where these properties were measured for a large population of wild-type rats and mice was also conducted. Given my findings, it was determined that for the most complete understanding of small animal bone it was necessary to measure strength and toughness. Strength measurements probe the flaw distribution and toughness measurements to evaluate the resistance to facture in the presence of a single dominant worst-case flaw.

  7. Mechanisms of, and Adjuvants for, Bone Pain.

    Science.gov (United States)

    Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

    2018-06-01

    Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

    Science.gov (United States)

    Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

    1997-01-01

    Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone

  9. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  10. New mechanisms and targets in the treatment of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2007-01-01

    Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

  11. Physiological role of growth factors and bone morphogenetic proteins in osteogenesis and bone fracture healing: а review

    Directory of Open Access Journals (Sweden)

    S. Sagalovsky

    2015-01-01

    Full Text Available The repair of large bone defects remains a major clinical orthopedic challenge. Bone regeneration and fracture healing is a complex physiological mechanisms regulated by a large number of biologically active molecules. Multiple factors regulate this cascade of molecular events, which affects different stages in the osteoblast and chondroblast lineage during such processes as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. A recent review has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to identification of many signaling molecules associated with formation of skeletal tissues, including a large family of growth factors (transforming growth factor-β and bone morphogenetic proteins, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived growth factor, cytokines and interleukins. There is increasing evidence indicating that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and bone mineralization. A clear understanding of cellular and molecular pathways involved in fracture healing is not only critical for improvement of fracture treatments, but it may also enhance further our knowledge of mechanisms involved in skeletal growth and repair, as well as mechanisms of aging. This suggests that, in the future, they may play a major role in the treatment of bone disease and fracture repair.

  12. Enhancement of bone formation in rabbits by recombinant human growth hormone

    International Nuclear Information System (INIS)

    Ehrnberg, A.; Brosjoe, O.; Laaftman, P.; Nilsson, O.; Stroemberg, L.

    1993-01-01

    We studied the effect of human recombinant growth hormone on diaphyseal bone in 40 adult rabbits. The diaphyseal periosteum of one femur in each animal was mechanically stimulated by a nylon cerclage band. The bands induced an increase in bone formation, bone mineral content, and maximum torque capacity of the diaphyseal bone at 1 and 2 months. Growth hormone enhanced the anabolic effect of the cerclage bands on bone metabolism, evidenced by a further increase in torsional strength of the femurs. (au) (32 refs.)

  13. Diamond as a scaffold for bone growth.

    Science.gov (United States)

    Fox, Kate; Palamara, Joseph; Judge, Roy; Greentree, Andrew D

    2013-04-01

    Diamond is an attractive material for biomedical implants. In this work, we investigate its capacity as a bone scaffold. It is well established that the bioactivity of a material can be evaluated by examining its capacity to form apatite-like calcium phosphate phases on its surface when exposed to simulated body fluid. Accordingly, polycrystalline diamond (PCD) and ultrananocrystalline diamond (UNCD) deposited by microwave plasma chemical vapour deposition were exposed to simulated body fluid and assessed for apatite growth when compared to the bulk silicon. Scanning electron microscopy and X-ray photoelectron spectroscopy showed that both UNCD and PCD are capable of acting as a bone scaffold. The composition of deposited apatite suggests that UNCD and PCD are suitable for in vivo implantation with UNCD possible favoured in applications where rapid osseointegration is essential.

  14. Mechanical Intervention for Maintenance of Cartilage and Bone

    Directory of Open Access Journals (Sweden)

    Hui B. Sun

    2011-01-01

    Full Text Available Mechanical loading provides indispensible stimuli for growth and development of the articular cartilage and bone. Interestingly, depending on loading conditions loads applied to the joint can be beneficial as well as harmful to skeletal maintenance and remodeling. Moderate loads to the synovial joint, for instance, suppress the expression levels of matrix metallproteinases (MMPs, while loads above a threshold tend to increase their destructive activities. This report focuses on two recently developed loading modalities from animal studies, joint motion and joint loading. Their unique characteristics and potential usages for maintenance of the articular cartilage and stimulation of bone remodeling are reviewed. Also described are biophysical and molecular mechanisms which likely are responsible for the load-driven maintenance of cartilage and bone, and a possibility of developing load-mediated treatments of osteoporosis and osteoarthritis.

  15. Mechanisms of Bone Resorption in Periodontitis

    Directory of Open Access Journals (Sweden)

    Stefan A. Hienz

    2015-01-01

    Full Text Available Alveolar bone loss is a hallmark of periodontitis progression and its prevention is a key clinical challenge in periodontal disease treatment. Bone destruction is mediated by the host immune and inflammatory response to the microbial challenge. However, the mechanisms by which the local immune response against periodontopathic bacteria disturbs the homeostatic balance of bone formation and resorption in favour of bone loss remain to be established. The osteoclast, the principal bone resorptive cell, differentiates from monocyte/macrophage precursors under the regulation of the critical cytokines macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. TNF-α, IL-1, and PGE2 also promote osteoclast activity, particularly in states of inflammatory osteolysis such as those found in periodontitis. The pathogenic processes of destructive inflammatory periodontal diseases are instigated by subgingival plaque microflora and factors such as lipopolysaccharides derived from specific pathogens. These are propagated by host inflammatory and immune cell influences, and the activation of T and B cells initiates the adaptive immune response via regulation of the Th1-Th2-Th17 regulatory axis. In summary, Th1-type T lymphocytes, B cell macrophages, and neutrophils promote bone loss through upregulated production of proinflammatory mediators and activation of the RANK-L expression pathways.

  16. The Multifactorial role of Peripheral Nervous System in Bone Growth

    Science.gov (United States)

    Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

    2017-09-01

    Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

  17. Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2014-09-01

    Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

  18. Long bone histology and growth patterns in ankylosaurs: implications for life history and evolution.

    Directory of Open Access Journals (Sweden)

    Martina Stein

    Full Text Available The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone.

  19. Growth Mechanism of Microbial Colonies

    Science.gov (United States)

    Zhu, Minhui; Martini, K. Michael; Kim, Neil H.; Sherer, Nicholas; Lee, Jia Gloria; Kuhlman, Thomas; Goldenfeld, Nigel

    Experiments on nutrient-limited E. coli colonies, growing on agar gel from single cells reveal a power-law distribution of sizes, both during the growth process and in the final stage when growth has ceased. We developed a Python simulation to study the growth mechanism of the bacterial population and thus understand the broad details of the experimental findings. The simulation takes into account nutrient uptake, metabolic function, growth and cell division. Bacteria are modeled in two dimensions as hard circle-capped cylinders with steric interactions and elastic stress dependent growth characteristics. Nutrient is able to diffuse within and between the colonies. The mechanism of microbial colony growth involves reproduction of cells within the colonies and the merging of different colonies. We report results on the dynamic scaling laws and final state size distribution, that capture in semi-quantitative detail the trends observed in experiment. Supported by NSF Grant 0822613.

  20. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J.; Partridge, Nicola C.

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  1. Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses.

    Science.gov (United States)

    Sun, Ling; Sucosky, Philippe

    2015-06-26

    To explore ex vivo the role of bone morphogenetic protein-4 (BMP-4) and transforming growth factor-beta1 (TGF-β1) in acute valvular response to fluid shear stress (FSS) abnormalities. Porcine valve leaflets were subjected ex vivo to physiologic FSS, supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 h in a double-sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-β1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin, and TGF-β1 or the TGF-β1 inhibitor SB-431542, respectively. Fresh porcine leaflets were used as controls. Each experimental group consisted of six leaflet samples. Immunostaining and immunoblotting were performed to assess endothelial activation in terms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions, paracrine signaling in terms of BMP-4 and TGF-β1 expressions and extracellular matrix (ECM) remodeling in terms of cathepsin L, cathepsin S, metalloproteinases (MMP)-2 and MMP-9 expressions. Immunostained images were quantified by normalizing the intensities of positively stained regions by the number of cells in each image while immunoblots were quantified by densitometry. Regardless of the culture medium, physiologic FSS maintained valvular homeostasis. Tissue exposure to supra-physiologic FSS magnitude in standard medium stimulated paracrine signaling (TGF-β1: 467% ± 22% vs 100% ± 6% in fresh controls, BMP-4: 258% ± 22% vs 100% ± 4% in fresh controls; P 0.05). Supra-physiologic FSS frequency had no effect on endothelial activation and paracrine signaling regardless of the culture medium but TGF-β1 silencing attenuated FSS-induced ECM degradation via MMP-9 downregulation (MMP-9: 302% ± 182% vs 100% ± 42% in fresh controls; P > 0.05). Valvular tissue is sensitive

  2. Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

    Science.gov (United States)

    Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

    2014-12-01

    Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. [Research advances of fluid bio-mechanics in bone].

    Science.gov (United States)

    Chen, Zebin; Huo, Bo

    2017-04-01

    It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

  4. THE STRUCTURAL AND MECHANICAL PROPERTIES OF THE BONE

    Directory of Open Access Journals (Sweden)

    Robert Karpiński

    2017-06-01

    Full Text Available The work contains basic information on the anatomy and physiology of bone tissue. Basic concepts related to the structure of bone tissue are presented. General issues related to bone reconstruction processes and biomechanical structural adaptations processes were described. Mechanical parameters of bone tissue were presented.

  5. Gut microbiota induce IGF-1 and promote bone formation and growth

    Science.gov (United States)

    Yan, Jing; Herzog, Jeremy W.; Tsang, Kelly; Brennan, Caitlin A.; Bower, Maureen A.; Garrett, Wendy S.; Sartor, Balfour R.; Charles, Julia F.

    2016-01-01

    Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth. PMID:27821775

  6. Effects of Phlomis umbrosa Root on Longitudinal Bone Growth Rate in Adolescent Female Rats

    Directory of Open Access Journals (Sweden)

    Donghun Lee

    2016-04-01

    Full Text Available This study aimed to investigate the effects of Phlomis umbrosa root on bone growth and growth mediators in rats. Female adolescent rats were administered P. umbrosa extract, recombinant human growth hormone or vehicle for 10 days. Tetracycline was injected intraperitoneally to produce a glowing fluorescence band on the newly formed bone on day 8, and 5-bromo-2′-deoxyuridine was injected to label proliferating chondrocytes on days 8–10. To assess possible endocrine or autocrine/paracrine mechanisms, we evaluated insulin-like growth factor-1 (IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3 or bone morphogenetic protein-2 (BMP-2 in response to P. umbrosa administration in either growth plate or serum. Oral administration of P. umbrosa significantly increased longitudinal bone growth rate, height of hypertrophic zone and chondrocyte proliferation of the proximal tibial growth plate. P. umbrosa also increased serum IGFBP-3 levels and upregulated the expressions of IGF-1 and BMP-2 in growth plate. In conclusion, P. umbrosa increases longitudinal bone growth rate by stimulating proliferation and hypertrophy of chondrocyte with the increment of circulating IGFBP-3. Regarding the immunohistochemical study, the effect of P. umbrosa may also be attributable to upregulation of local IGF-1 and BMP-2 expressions in the growth plate, which can be considered as a GH dependent autocrine/paracrine pathway.

  7. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  8. An adaptation model for trabecular bone at different mechanical levels

    Directory of Open Access Journals (Sweden)

    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  9. Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance.

    Science.gov (United States)

    Stern, Tomer; Aviram, Rona; Rot, Chagai; Galili, Tal; Sharir, Amnon; Kalish Achrai, Noga; Keller, Yosi; Shahar, Ron; Zelzer, Elazar

    2015-08-01

    One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of

  10. Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance

    Science.gov (United States)

    Stern, Tomer; Aviram, Rona; Rot, Chagai; Galili, Tal; Sharir, Amnon; Kalish Achrai, Noga; Keller, Yosi; Shahar, Ron; Zelzer, Elazar

    2015-01-01

    One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of

  11. Bone growth and turnover in progesterone receptor knockout mice.

    Energy Technology Data Exchange (ETDEWEB)

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O' Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  12. Biocompatibility of calcium phosphate bone cement with optimised mechanical properties: an in vivo study.

    Science.gov (United States)

    Palmer, Iwan; Nelson, John; Schatton, Wolfgang; Dunne, Nicholas J; Buchanan, Fraser; Clarke, Susan A

    2016-12-01

    This work establishes the in vivo performance of modified calcium phosphate bone cements for vertebroplasty of spinal fractures using a lapine model. A non-modified calcium phosphate bone cement and collagen-calcium phosphate bone cements composites with enhanced mechanical properties, utilising either bovine collagen or collagen from a marine sponge, were compared to a commercial poly(methyl methacrylate) cement. Conical cement samples (8 mm height × 4 mm base diameter) were press-fit into distal femoral condyle defects in New Zealand White rabbits and assessed after 5 and 10 weeks. Bone apposition and tartrate-resistant acid phosphatase activity around cements were assessed. All implants were well tolerated, but bone apposition was higher on calcium phosphate bone cements than on poly(methyl methacrylate) cement. Incorporation of collagen showed no evidence of inflammatory or immune reactions. Presence of positive tartrate-resistant acid phosphatase staining within cracks formed in calcium phosphate bone cements suggested active osteoclasts were present within the implants and were actively remodelling within the cements. Bone growth was also observed within these cracks. These findings confirm the biological advantages of calcium phosphate bone cements over poly(methyl methacrylate) and, coupled with previous work on enhancement of mechanical properties through collagen incorporation, suggest collagen-calcium phosphate bone cement composite may offer an alternative to calcium phosphate bone cements in applications where low setting times and higher mechanical stability are important.

  13. The effects of oestrogens on linear bone growth

    DEFF Research Database (Denmark)

    Juul, A

    2001-01-01

    Regulation of linear bone growth in children and adolescents comprises a complex interaction of hormones and growth factors. Growth hormone (GH) is considered to be the key hormone regulator of linear growth in childhood. The pubertal increase in growth velocity associated with GH has traditionally...... been attributed to testicular androgen secretion in boys, and to oestrogens or adrenal androgen secretion in girls. Research data indicating that oestrogen may be the principal hormone stimulating the pubertal growth spurt in boys as well as girls is reviewed. Such an action is mediated by oestrogen...... female growth spurt despite lack of androgen action. Oestrogens may also influence linear bone growth indirectly via modulation of the GH-insulin-like growth factor-I (IGF-I) axis. Thus, ER blockade diminishes endogenous GH secretion, androgen receptor (AR) blockade increases GH secretion in peripubertal...

  14. Bone Quality: The Mechanical Effects of Microarchitecture and Matrix Properties

    NARCIS (Netherlands)

    J.S. Day (Judd)

    2005-01-01

    textabstractIn this body of work we have examined some of the current concepts pertaining to the relation between bone mass, bone quality and the mechanical properties of bone. In our first series of studies we used a model of human osteoarthritis to investigate the implications of changes in the

  15. 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

  16. Maxillary sinus lift with solely autogenous bone compared to a combination of autogenous bone and growth factors or (solely) bone substitutes. A systematic review : a systematic review

    NARCIS (Netherlands)

    Rickert, D.; Slater, J. J. R. Huddleston; Meijer, H. J. A.; Vissink, A.; Raghoebar, G. M.

    Literature regarding the outcome of maxillary sinus floor elevation to create sufficient bone fraction to enable implant placement was systematically reviewed. Bone fraction and implant survival rate were assessed to determine whether grafting material or applied growth factor affected bone

  17. Introduction to skeletal radiology and bone growth

    International Nuclear Information System (INIS)

    Rogers, L.F.

    1987-01-01

    Radiographic examination is the key to the diagnosis of many skeletal abnormalities. It is essential that each bone be examined in its entirety, including the cortex, medullary canal (cancellous bone or spongiosa), and articular ends. The position and alignment of joints are determined. In children, the epiphysis and epiphyseal line or physis must be observed. The adjacent soft tissues are examined. Obliteration of normal soft-tissue lines and the presence of a joint effusion are of particular importance. When disease is present, it is important to determine whether the process is limited to a single bone or joint or whether multiple bones or joints are involved. The distribution of disease is also a consideration. The presence and type of bone destruction and bone production, the appearance of the edges or borders of the lesion, and the presence or absence of cortical expansion and periosteal reaction are also noted. The radiographic findings are then correlated with the clinical history and the age and sex of the patient to arrive at a logical diagnosis. The diagnosis may be firm in some instances; in other cases, a differential diagnosis is offered since the exact diagnosis cannot be determined

  18. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

    Science.gov (United States)

    Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

    2014-01-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

  19. Novel mechanically competent polysaccharide scaffolds for bone tissue engineering

    International Nuclear Information System (INIS)

    Kumbar, S G; Toti, U S; Deng, M; James, R; Laurencin, C T; Aravamudhan, A; Harmon, M; Ramos, D M

    2011-01-01

    The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their β-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three-dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10–15% after 24 weeks. A typical stress–strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid–glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration.

  20. Mechanical response tissue analyzer for estimating bone strength

    Science.gov (United States)

    Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

    1991-01-01

    One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

  1. [Growth rate and bone maturation in celiac disease (author's transl)].

    Science.gov (United States)

    Martínez Sopena, M J; Calvo Romero, M C; Bedate Calderón, P; Alonso Franch, M; Sánchez Villares, E

    1978-05-01

    The growth and bone maturation of 43 celiac patients were analyzed. A significant correlation between gluten intake and growth rate was found. The authors suggest this is a good parameter to advise the best moment to make the control biopsie and the provocation test.

  2. Prediction of mechanical properties of trabecular bone using quantitative MRI

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  3. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Role and mechanism of action of Sclerostin in bone

    Science.gov (United States)

    Delgado-Calle, Jesus; Sato, Amy Y.; Bellido, Teresita

    2016-01-01

    After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone. Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin. However, the anabolic effect of blocking sclerostin decreases with time, bone mass accrual is also accompanied by anti-catabolic effects, and there is bone loss over time after therapy discontinuation. Further, the cellular source of sclerostin in the bone/bone marrow microenvironment under physiological and pathological conditions, the pathways that regulate sclerostin expression and the mechanisms by which sclerostin modulates the activity of osteocytes, osteoblasts, and osteoclasts remain unclear. In this review, we highlight the current knowledge on the regulation of Sost/sclerotin expression and its mechanism(s) of action, discuss novel observations regarding its role in signaling pathways activated by hormones and mechanical stimuli in bone, and propose future research needed to understand the full potential of therapeutic interventions that modulate Sost/sclerostin expression. PMID:27742498

  5. Regulation of Long Bone Growth in Vertebrates; It Is Time to Catch Up.

    Science.gov (United States)

    Roselló-Díez, Alberto; Joyner, Alexandra L

    2015-12-01

    The regulation of organ size is essential to human health and has fascinated biologists for centuries. Key to the growth process is the ability of most organs to integrate organ-extrinsic cues (eg, nutritional status, inflammatory processes) with organ-intrinsic information (eg, genetic programs, local signals) into a growth response that adapts to changing environmental conditions and ensures that the size of an organ is coordinated with the rest of the body. Paired organs such as the vertebrate limbs and the long bones within them are excellent models for studying this type of regulation because it is possible to manipulate one member of the pair and leave the other as an internal control. During development, growth plates at the end of each long bone produce a transient cartilage model that is progressively replaced by bone. Here, we review how proliferation and differentiation of cells within each growth plate are tightly controlled mainly by growth plate-intrinsic mechanisms that are additionally modulated by extrinsic signals. We also discuss the involvement of several signaling hubs in the integration and modulation of growth-related signals and how they could confer remarkable plasticity to the growth plate. Indeed, long bones have a significant ability for "catch-up growth" to attain normal size after a transient growth delay. We propose that the characterization of catch-up growth, in light of recent advances in physiology and cell biology, will provide long sought clues into the molecular mechanisms that underlie organ growth regulation. Importantly, catch-up growth early in life is commonly associated with metabolic disorders in adulthood, and this association is not completely understood. Further elucidation of the molecules and cellular interactions that influence organ size coordination should allow development of novel therapies for human growth disorders that are noninvasive and have minimal side effects.

  6. The acrophysis: a unifying concept for enchondral bone growth and its disorders. I. Normal growth

    International Nuclear Information System (INIS)

    Oestreich, Alan E.

    2003-01-01

    In order to discuss and illustrate the common effects on normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' is proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the non-physeal ends of small tubular bones. The last layer of development of both physes and acrophysis is the cartilaginous zone of provisional calcification (ZPC). The enchondral bone abutting the ZPC shares similar properties at physes and acrophyses, including the relatively lucent metaphyseal bands of many normal infants at several weeks of age. The bone-in-bone pattern of the normal vertebral bodies and bands of demineralization of the tarsal bones just under the ZPC are the equivalent of those bands. The growth arrest/recovery lines of metaphyses similarly have equivalent lines in growth centers and other acrophyseal sites. Nearly the same effects can also be anticipated from the relatively similar growth plate at the cartilaginous cap of benign exostoses (''paraphysis''). The companion article will explore abnormalities at acrophyseal sites, including metabolic bone disease and dysplasias. (orig.)

  7. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  8. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Electric reaction arising in bone subjected to mechanical loadings

    Science.gov (United States)

    Murasawa, Go; Cho, Hideo; Ogawa, Kazuma

    2006-03-01

    The aim of present study is the investigation of the electric reaction arising in bone subjected to mechanical loadings. Firstly, specimen was fabricated from femur of cow, and ultrasonic propagation in bone was measured by ultrasonic technique. Secondary, 4-point bending test was conducted up to fracture, and electric reaction arising in bone was measured during loading. Thirdly, cyclic 4-point bending test was conducted to investigate the effect of applied displacement speed on electric reaction.

  11. Regulation of chick bone growth by leptin and catecholamines.

    Science.gov (United States)

    Mauro, L J; Wenzel, S J; Sindberg, G M

    2010-04-01

    Leptin and the sympathetic nervous system have a unique role in linking nutritional status to skeletal metabolism in mammals. Such a regulatory mechanism has not been identified in birds but would be beneficial to signal information about energy reserves to an organ system essential for locomotion, reproduction, and survival. To explore this potential role of leptin and the sympathetic nervous system in birds, an ex vivo chick tibiotarsal model was used to test the effects of leptin and sympathetic activity on longitudinal bone growth and the expression of chondrocyte markers. Reverse transcription-PCR analysis revealed the expression of chicken leptin receptor mRNA as well as both alpha-adrenergic (alpha1A, alpha2A, alpha2B, alpha2C) and beta adrenergic (beta1, beta2) receptor subtype mRNA in the whole bone. Incubation with norepinephrine (NE; 0, 10, or 100 microM for 4 d) caused a significant increase in distal condyle length as compared with vehicle-treated, contralateral tibiotarsi. In contrast, no change in condyle length was detected after leptin treatment (0 or 10 nM or 1 microM for 4 d). Analysis of cell proliferation by bromodeoxyuridine incorporation revealed no increase in bromodeoxyuridine-positive cells in the condyles in response to leptin or NE treatments. Real-time PCR analysis showed that NE enhanced type X collagen mRNA expression, a marker of mature hypertrophic chondrocytes, with no effect on type II collagen mRNA, the matrix protein secreted by proliferating chondrocytes. Leptin treatment had no effect on the expression of either matrix protein. Treatment with agonists specific for alpha- or beta-adrenergic receptors indicates that the activation of alpha-adrenergic receptors is most likely responsible for the sympathetic effect on type X collagen gene expression. These results suggest that NE and other sympathetic agonists have positive effects on bone elongation and the changes in critical genes associated with this process. These

  12. Focus on growth hormone deficiency and bone in adults.

    Science.gov (United States)

    Tritos, Nicholas A

    2017-02-01

    Growth hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth hormone deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18-24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  14. Bone scaffolds with homogeneous and discrete gradient mechanical properties.

    Science.gov (United States)

    Jelen, C; Mattei, G; Montemurro, F; De Maria, C; Mattioli-Belmonte, M; Vozzi, G

    2013-01-01

    Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a carrier or template for implanted bone cells or other agents. We prepared different bone tissue constructs based on collagen, gelatin and hydroxyapatite using genipin as cross-linking agent. The fabricated construct did not present a release neither of collagen neither of genipin over its toxic level in the surrounding aqueous environment. Each scaffold has been mechanically characterized with compression, swelling and creep tests, and their respective viscoelastic mechanical models were derived. Mechanical characterization showed a practically elastic behavior of all samples and that compressive elastic modulus basically increases as content of HA increases, and it is strongly dependent on porosity and water content. Moreover, by considering that gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues, we developed discrete functionally graded scaffolds (discrete FGSs) in order to mimic the graded structure of bone tissue. These new structures were mechanically characterized showing a marked anisotropy as the native bone tissue. Results obtained have shown FGSs could represent valid bone substitutes. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. The effects of oestrogens on linear bone growth

    DEFF Research Database (Denmark)

    Juul, A

    2001-01-01

    receptors (ER-alpha and ER-beta) in the human growth plate, and polymorphisms in the ER gene may influence adult height in healthy subjects. Prepubertal oestradiol concentrations are significantly higher in girls than in boys, explaining sex-related differences in pubertal onset. Men with a disruptive......Regulation of linear bone growth in children and adolescents comprises a complex interaction of hormones and growth factors. Growth hormone (GH) is considered to be the key hormone regulator of linear growth in childhood. The pubertal increase in growth velocity associated with GH has traditionally...... been attributed to testicular androgen secretion in boys, and to oestrogens or adrenal androgen secretion in girls. Research data indicating that oestrogen may be the principal hormone stimulating the pubertal growth spurt in boys as well as girls is reviewed. Such an action is mediated by oestrogen...

  16. ALCOHOL AND BONE GROWTH: A Literary Appraisal II

    African Journals Online (AJOL)

    user

    the agent ii, Maternal-embryonic exchange and iii,. The genotype ... drug is administered to the pregnant animal .... experimentally induced congenital skeletal defects in rat were achieved with a nutrient deficient treatment. This discovery was rather accidental, because .... the stem cells in the growth plates of long bones are.

  17. The Mechanics of Long Bone Fractures.

    Science.gov (United States)

    1981-01-31

    r = .99) between wet density and ultimate bending strength for 37 specimens of human femoral bone. Evans (1973) studied embalmed human tibial...Work 2 2.2 Methods 6 2.2.1 Torsional Loading 6 2.2.2 The Effects of Combined Loading 10 2.2.3 Cancellous Bone Effects 11 2.3 Results 11 2.3.1...PROPERTIES 21 3.1 Previous Work 22 3.2 Methods 26 3.2.1 Cross Sectional Property Software 26 3.2.2 CT Scanning Procedure 28 3.2.3 Linear Dependency of

  18. Nonlinear pattern formation in bone growth and architecture

    Directory of Open Access Journals (Sweden)

    Phil eSalmon

    2015-01-01

    Full Text Available The 3D morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatio-temporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here – chaotic nonlinear pattern formation (NPF – which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of group intelligence exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called particle swarm optimization (PSO. This theoretical model could be applicable to the behavior of osteoblasts osteoclasts and osteocytes, seeing them operating socially in response simultaneously to both global and local signals (endocrine, cytokine, mechanical resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in-silico simulation of bone modeling.What insights has NPF provided to bone biology? One example concerns the genetic disorder Juvenile Pagets Disease (JPD or Idiopathic Hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here coupling or feedback between osteoblasts and osteoclasts is the critical element.This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent consequence of the

  19. Non-linear pattern formation in bone growth and architecture.

    Science.gov (United States)

    Salmon, Phil

    2014-01-01

    The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here - chaotic non-linear pattern formation (NPF) - which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of "group intelligence" exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called "particle swarm optimization" (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating "socially" in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or "feedback" between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent

  20. Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

    International Nuclear Information System (INIS)

    Maldonado, Solvey; Findeisen, Rolf

    2010-01-01

    The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

  1. Molecular mechanisms of crystal growth

    International Nuclear Information System (INIS)

    Pina, C. M.

    2000-01-01

    In this paper I present an example of the research that the Mineral Surface Group of the Munster University is conducting in the field of Crystal Growth. Atomic Force Microscopy (Am) in situ observations of different barite (BaSO4) faces growing from aqueous solutions, in combination with computer simulations of the surface attachment of growth units allows us to test crystal growth models. Our results demonstrate the strong structural control that a crystal can exert on its own growth, revealing also the limitation of the classical crystal growth theories (two dimensional nucleation and spiral growth models) in providing a complete explanation for the growth behaviour at a molecular scale. (Author) 6 refs

  2. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    OpenAIRE

    Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

    2013-01-01

    Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

  3. Functional Diversity of Fibroblast Growth Factors in Bone Formation

    Directory of Open Access Journals (Sweden)

    Yuichiro Takei

    2015-01-01

    Full Text Available The functional significance of fibroblast growth factor (FGF signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs. Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.

  4. ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Rudkjaer, Lise

    2006-01-01

    ADAM12-S transgenic mice exhibit a pronounced increase in the length of bones, such as femur, tibia, and vertebrae. The effect of ADAM12-S on longitudinal bone growth involves the modulation of chondrocyte proliferation and maturation, likely through proteolytic activities and altered cell......: Transgenic mice expressing the secreted form of human ADAM12, ADAM12-S, or a truncated metalloprotease-deficient form of ADAM12-S in the circulation were used to study the effects of ADAM12 on the skeleton. In addition, murine chondrocyte cultures were used to study the effect of ADAM12-S on cell...... studies showed that ADAM12-S inhibits chondrocyte adhesion to fibronectin and collagen type II. CONCLUSIONS: ADAM12-S stimulates bone growth in mice by modulating chondrocyte proliferation and maturation through mechanisms probably involving both metalloprotease and adhesion activities....

  5. Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

    Directory of Open Access Journals (Sweden)

    Jason A Bleedorn

    Full Text Available Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK, phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt, and mammalian target of rapamycin (mTOR. However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK's, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α, brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, c-jun, and c-fos in dorsal root ganglion (DRG of the brachial intumescence were performed. There was a significant increase in signaling through MAPK's including extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05. However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the

  6. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  7. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-01-01

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα ColII , expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα ColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα ColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα ColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  8. The chondrocytic journey in endochondral bone growth and skeletal dysplasia.

    Science.gov (United States)

    Yeung Tsang, Kwok; Wa Tsang, Shun; Chan, Danny; Cheah, Kathryn S E

    2014-03-01

    The endochondral bones of the skeleton develop from a cartilage template and grow via a process involving a cascade of chondrocyte differentiation steps culminating in formation of a growth plate and the replacement of cartilage by bone. This process of endochondral ossification, driven by the generation of chondrocytes and their subsequent proliferation, differentiation, and production of extracellular matrix constitute a journey, deviation from which inevitably disrupts bone growth and development, and is the basis of human skeletal dysplasias with a wide range of phenotypic severity, from perinatal lethality to progressively deforming. This highly coordinated journey of chondrocyte specification and fate determination is controlled by a myriad of intrinsic and extrinsic factors. SOX9 is the master transcription factor that, in concert with varying partners along the way, directs the different phases of the journey from mesenchymal condensation, chondrogenesis, differentiation, proliferation, and maturation. Extracellular signals, including bone morphogenetic proteins, wingless-related MMTV integration site (WNT), fibroblast growth factor, Indian hedgehog, and parathyroid hormone-related peptide, are all indispensable for growth plate chondrocytes to align and organize into the appropriate columnar architecture and controls their maturation and transition to hypertrophy. Chondrocyte hypertrophy, marked by dramatic volume increase in phases, is controlled by transcription factors SOX9, Runt-related transcription factor, and FOXA2. Hypertrophic chondrocytes mediate the cartilage to bone transition and concomitantly face a live-or-die situation, a subject of much debate. We review recent insights into the coordination of the phases of the chondrocyte journey, and highlight the need for a systems level understanding of the regulatory networks that will facilitate the development of therapeutic approaches for skeletal dysplasia. Copyright © 2014 Wiley Periodicals

  9. The ultrastructure of bone and its relevance to mechanical properties

    Science.gov (United States)

    Schwarcz, Henry P.; Abueidda, Diab; Jasiuk, Iwona

    2017-09-01

    Bone is a biologically generated composite material comprised of two major structural components: crystals of apatite and collagen fibrils. Computational analysis of the mechanical properties of bone must make assumptions about the geometric and topological relationships between these components. Recent transmission electron microscope (TEM) studies of samples of bone prepared using ion milling methods have revealed important previously unrecognized features in the ultrastructure of bone. These studies show that most of the mineral in bone lies outside the fibrils and is organized into elongated plates 5 nanometers (nm) thick, 80 nm wide and hundreds of nm long. These so-called mineral lamellae (MLs) are mosaics of single 5 nm-thick, 20 - 50 nm wide crystals bonded at their edges. MLs occur either stacked around the 50 nm-diameter collagen fibrils, or in parallel stacks of 5 or more MLs situated between fibrils. About 20% of mineral is in gap zones within the fibrils. MLs are apparently glued together into mechanically coherent stacks which break across the stack rather than delaminating. ML stacks should behave as cohesive units during bone deformation. Finite element computations of mechanical properties of bone show that the model including such features generates greater stiffness and strength than are obtained using conventional models in which most of the mineral, in the form of isolated crystals, is situated inside collagen fibrils.

  10. Elastic-plastic fracture mechanics of compact bone

    Science.gov (United States)

    Yan, Jiahau

    Bone is a composite composed mainly of organics, minerals and water. Most studies on the fracture toughness of bone have been conducted at room temperature. Considering that the body temperature of animals is higher than room temperature, and that bone has a high volumetric percentage of organics (generally, 35--50%), the effect of temperature on fracture toughness of bone should be studied. Single-edged V-shaped notched (SEVN) specimens were prepared to measure the fracture toughness of bovine femur and manatee rib in water at 0, 10, 23, 37 and 50°C. The fracture toughness of bovine femur and manatee rib were found to decrease from 7.0 to 4.3 MPa·m1/2 and from 5.5 to 4.1 MPa·m1/2, respectively, over a temperature range of 50°C. The decreases were attributed to inability of the organics to sustain greater stresses at higher temperatures. We studied the effects of water and organics on fracture toughness of bone using water-free and organics-free SEVN specimens at 23°C. Water-free and organics-free specimens were obtained by placing fresh bone specimen in a furnace at different temperatures. Water and organics significantly affected the fracture toughness of bone. Fracture toughness of the water-free specimens was 44.7% (bovine femur) and 32.4% (manatee rib) less than that of fresh-bone specimens. Fracture toughness of the organics-free specimens was 92.7% (bovine femur) and 91.5% (manatee rib) less than that of fresh bone specimens. Linear Elastic Fracture Mechanics (LEFM) is widely used to study bone. However, bone often has small to moderate scale yielding during testing. We used J integral, an elastic-plastic fracture-mechanics parameter, to study the fracture process of bone. The J integral of bovine femur increased from 6.3 KJ/mm2 at 23°C to 6.7 KJ/mm2 at 37°C. Although the fracture toughness of bovine bone decreases as the temperature increases, the J integral results show a contrary trend. The energy spent in advancing the crack beyond the linear

  11. Mechanisms of diabetes mellitus-induced bone fragility

    DEFF Research Database (Denmark)

    Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D

    2017-01-01

    The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM...... and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia......-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus....

  12. Collagen and mineral deposition in rabbit cortical bone during maturation and growth: effects on tissue properties.

    Science.gov (United States)

    Isaksson, Hanna; Harjula, Terhi; Koistinen, Arto; Iivarinen, Jarkko; Seppänen, Kari; Arokoski, Jari P A; Brama, Pieter A; Jurvelin, Jukka S; Helminen, Heikki J

    2010-12-01

    We characterized the composition and mechanical properties of cortical bone during maturation and growth and in adult life in the rabbit. We hypothesized that the collagen network develops earlier than the mineralized matrix. Growth was monitored, and the rabbits were euthanized at birth (newborn), and at 1, 3, 6, 9, and 18 months of age. The collagen network was assessed biochemically (collagen content, enzymatic and non-enzymatic cross-links) in specimens from the mid-diaphysis of the tibia and femur and biomechanically (tensile testing) from decalcified whole tibia specimens. The mineralized matrix was analyzed using pQCT and 3-point bend tests from intact femur specimens. The collagen content and the Young's modulus of the collagen matrix increased significantly until the rabbits were 3 months old, and thereafter remained stable. The amount of HP and LP collagen cross-links increased continuously from newborn to 18 months of age, whereas PEN cross-links increased after 6 months of age. Bone mineral density and the Young's modulus of the mineralized bone increased until the rabbits were at least 6 months old. We concluded that substantial changes take place during the normal process of development in both the biochemical and biomechanical properties of rabbit cortical bone. In cortical bone, the collagen network reaches its mature composition and mechanical strength prior to the mineralized matrix. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  13. Bone density and body composition in chronic renal failure: effects of growth hormone treatment

    NARCIS (Netherlands)

    van der Sluis, I. M.; Boot, A. M.; Nauta, J.; Hop, W. C.; de Jong, M. C.; Lilien, M. R.; Groothoff, J. W.; van Wijk, A. E.; Pols, H. A.; Hokken-Koelega, A. C.; de Muinck Keizer-Schrama, S. M.

    2000-01-01

    Metabolic bone disease and growth retardation are common complications of chronic renal failure (CRF). We evaluated bone mineral density (BMD), bone metabolism, body composition and growth in children with CRF, and the effect of growth hormone treatment (GHRx) on these variables. Thirty-three

  14. Mechanical design optimization of bioabsorbable fixation devices for bone fractures.

    Science.gov (United States)

    Lovald, Scott T; Khraishi, Tariq; Wagner, Jon; Baack, Bret

    2009-03-01

    Bioabsorbable bone plates can eliminate the necessity for a permanent implant when used to fixate fractures of the human mandible. They are currently not in widespread use because of the low strength of the materials and the requisite large volume of the resulting bone plate. The aim of the current study was to discover a minimally invasive bioabsorbable bone plate design that can provide the same mechanical stability as a standard titanium bone plate. A finite element model of a mandible with a fracture in the body region is subjected to bite loads that are common to patients postsurgery. The model is used first to determine benchmark stress and strain values for a titanium plate. These values are then set as the limits within which the bioabsorbable bone plate must comply. The model is then modified to consider a bone plate made of the polymer poly-L/DL-lactide 70/30. An optimization routine is run to determine the smallest volume of bioabsorbable bone plate that can perform and a titanium bone plate when fixating fractures of this considered type. Two design parameters are varied for the bone plate design during the optimization analysis. The analysis determined that a strut style poly-L-lactide-co-DL-lactide plate of 690 mm2 can provide as much mechanical stability as a similar titanium design structure of 172 mm2. The model has determined a bioabsorbable bone plate design that is as strong as a titanium plate when fixating fractures of the load-bearing mandible. This is an intriguing outcome, considering that the polymer material has only 6% of the stiffness of titanium.

  15. Growth plate closure: Apex view on bone scan

    International Nuclear Information System (INIS)

    Giles, P.H.; Trochei, M.; Yeates, K.

    1984-01-01

    Angular deformities of the extremities in children following premature closure of the growth plate are well known. The deformities depend on the position of an osseus bridge which forms between the epiphysis and metaphysis. Several surgical procedures including resection of the osseus bridge have been described, however, delineation of the site of fusion is difficult to define. The commonest site of growth plate arrest is the distal femoral or proximal tibial growth plate. A new technique using the bone scan has been developed which accurately defines the area and position of these osseus bridges. Two hours after injection of technetium 99m methylene diphosphonate apex views of the affected distal femoral growth plate were performed. The knee was flexed into its smallest angle. Using a pinhole collimator the gamma camera was angled to face the affected growth plate end on. The image was collected onto computer and analysed by: (I) regions of interest over segments of the growth plate to calculate the relative area of total growth plate affected: (II) generating histograms: (III) thresholding or performing isocontours to accentuate abnormal areas. The growth plate is normally uniformly increased when compared to the normal shaft of the bone. Fusion across the plate appears as an area of diminished uptake. The apex view gives a unique functional map of the growth plate such that abnormal areas are displayed, and the site, size and position of osseus fusion obtained. The technique has the potential for determining the metabolic activity of the growth plate before and after surgery. Serial studies will allow assessment of regneration of the plate and reformation of new osseus bridges

  16. The crack growth mechanism in asphaltic mixes

    NARCIS (Netherlands)

    Jacobs, M.M.J.; Hopman, P.C.; Molenaar, A.A.A.

    1995-01-01

    The crack growth mechanism in asphalt concrete (Ac) mixes is studied. In cyclic tests on several asphaltic mixes crack growth is measured, both with crack foils and with cOD-gauges. It is found that crack growth in asphaltic mixes is described by three processes which are parallel in time: cohesive

  17. Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

    Science.gov (United States)

    Yin, Fei; Meng, Chunyang; Lu, Rifeng; Li, Lei; Zhang, Ying; Chen, Hao; Qin, Yonggang; Guo, Li

    2014-01-01

    Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury. PMID:25374587

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

    Science.gov (United States)

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

    2012-11-01

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

  19. Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

    International Nuclear Information System (INIS)

    Bonnet, N.; Bernard, P.; Beaupied, H; Bizot, J.C.; Trovero, F.; Courteix, D.; Benhamou, C.L.

    2007-01-01

    The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg -1 day -1 of desipramine, fluoxetine or 10 mg kg -1 day -1 of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p -1 , 6431 ± 1182 MPa) than in placebo (101 ± 9 N mm -1 , 8441 ± 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone

  20. Non-rigid image registration using bone growth model

    DEFF Research Database (Denmark)

    Bro-Nielsen, Morten; Gramkow, Claus; Kreiborg, Sven

    1997-01-01

    Non-rigid registration has traditionally used physical models like elasticity and fluids. These models are very seldom valid models of the difference between the registered images. This paper presents a non-rigid registration algorithm, which uses a model of bone growth as a model of the change...... between time sequence images of the human mandible. By being able to register the images, this paper at the same time contributes to the validation of the growth model, which is based on the currently available medical theories and knowledge...

  1. Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

    Science.gov (United States)

    Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

    2016-09-01

    Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

  2. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  3. Mechanical properties of femoral trabecular bone in dogs

    Directory of Open Access Journals (Sweden)

    Nolte Ingo

    2005-03-01

    Full Text Available Abstract Background Studying mechanical properties of canine trabecular bone is important for a better understanding of fracture mechanics or bone disorders and is also needed for numerical simulation of canine femora. No detailed data about elastic moduli and degrees of anisotropy of canine femoral trabecular bone has been published so far, hence the purpose of this study was to measure the elastic modulus of trabecular bone in canine femoral heads by ultrasound testing and to assess whether assuming isotropy of the cancellous bone in femoral heads in dogs is a valid simplification. Methods From 8 euthanized dogs, both femora were obtained and cubic specimens were cut from the centre of the femoral head which were oriented along the main pressure and tension trajectories. The specimens were tested using a 100 MHz ultrasound transducer in all three orthogonal directions. The directional elastic moduli of trabecular bone tissue and degrees of anisotropy were calculated. Results The elastic modulus along principal bone trajectories was found to be 11.2 GPa ± 0.4, 10.5 ± 2.1 GPa and 10.5 ± 1.8 GPa, respectively. The mean density of the specimens was 1.40 ± 0.09 g/cm3. The degrees of anisotropy revealed a significant inverse relationship with specimen densities. No significant differences were found between the elastic moduli in x, y and z directions, suggesting an effective isotropy of trabecular bone tissue in canine femoral heads. Discussion This study presents detailed data about elastic moduli of trabecular bone tissue obtained from canine femoral heads. Limitations of the study are the relatively small number of animals investigated and the measurement of whole specimen densities instead of trabecular bone densities which might lead to an underestimation of Young's moduli. Publications on elastic moduli of trabecular bone tissue present results that are similar to our data. Conclusion This study provides data about directional elastic

  4. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-01-01

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  5. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  6. Effect of trehalose coating on basic fibroblast growth factor release from tailor-made bone implants.

    Science.gov (United States)

    Choi, Sungjin; Lee, Jongil; Igawa, Kazuyo; Suzuki, Shigeki; Mochizuki, Manabu; Nishimura, Ryohei; Chung, Ung-il; Sasaki, Nobuo

    2011-12-01

    Artificial bone implants are often incorporated with osteoinductive factors to facilitate early bone regeneration. Calcium phosphate, the main component in artificial bone implants, strongly binds these factors, and in a few cases, the incorporated proteins are not released from the implant under conditions of physiological pH, thereby leading to reduction in their osteoinductivity. In this study, we coated tailor-made bone implants with trehalose to facilitate the release of basic fibroblast growth factor (bFGF). In an in vitro study, mouse osteoblastic cells were separately cultured for 48 hr in a medium with a untreated implant (T-), trehalose-coated implant (T+), bFGF-incorporated implant (FT-), and bFGF-incorporated implant with trehalose coating (FT+). In the FT+ group, cell viability was significantly higher than that in the other groups (Pbone implant without affecting the crystallinity or the mechanical strength of the artificial bone implant. These results suggest that coating artificial bone implants with trehalose could limit the binding of bFGF to calcium phosphate.

  7. Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

    Science.gov (United States)

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

    2010-08-01

    Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells.

    Science.gov (United States)

    Hu, Minyi; Yeh, Robbin; Lien, Michelle; Teeratananon, Morgan; Agarwal, Kunal; Qin, Yi-Xian

    2013-03-01

    Osteoblasts are derived from mesenchymal stem cells (MSCs), which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily "10 min on-5 min off-10 min on" loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteoporosis treatments.

  9. Rac1 Dosage Is Crucial for Normal Endochondral Bone Growth.

    Science.gov (United States)

    Suzuki, Dai; Bush, Jason R; Bryce, Dawn-Marie; Kamijo, Ryutaro; Beier, Frank

    2017-10-01

    Rac1, a member of the small Rho GTPase family, plays multiple cellular roles. Studies of mice conditionally lacking Rac1 have revealed essential roles for Rac1 in various tissues, including cartilage and limb mesenchyme, where Rac1 loss produces dwarfism and long bone shortening. To gain further insight into the role of Rac1 in skeletal development, we have used transgenic mouse lines to express a constitutively active (ca) Rac1 mutant protein in a Cre recombinase-dependent manner. Overexpression of caRac1 in limb bud mesenchyme or chondrocytes leads to reduced body weight and shorter bones compared with control mice. Histological analysis of growth plates showed that caRac1;Col2-Cre mice displayed ectopic hypertrophic chondrocytes in the proliferative zone and enlarged hypertrophic zones. These mice also displayed a reduced proportion of proliferating cell nuclear antigen-positive cells in the proliferative zone and nuclear β-catenin localization in the ectopic hypertrophic chondrocytes. Importantly, overexpression of caRac1 partially rescued the phenotypes of Rac1fl/fl;Col2-Cre and Rac1fl/fl;Prx1-Cre conditional knockout mice, including body weight, bone length, and growth plate disorganization. These results suggest that tight regulation of Rac1 activity is necessary for normal cartilage development. Copyright © 2017 Endocrine Society.

  10. Early mechanical stimulation only permits timely bone healing in sheep.

    Science.gov (United States)

    Tufekci, Pelin; Tavakoli, Aramesh; Dlaska, Constantin; Neumann, Mirjam; Shanker, Mihir; Saifzadeh, Siamak; Steck, Roland; Schuetz, Michael; Epari, Devakar

    2018-06-01

    Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors.

    Science.gov (United States)

    Font Tellado, Sonia; Balmayor, Elizabeth R; Van Griensven, Martijn

    2015-11-01

    Integration between tendon/ligament and bone occurs through a specialized tissue interface called enthesis. The complex and heterogeneous structure of the enthesis is essential to ensure smooth mechanical stress transfer between bone and soft tissues. Following injury, the interface is not regenerated, resulting in high rupture recurrence rates. Tissue engineering is a promising strategy for the regeneration of a functional enthesis. However, the complex structural and cellular composition of the native interface makes enthesis tissue engineering particularly challenging. Thus, it is likely that a combination of biomaterials and cells stimulated with appropriate biochemical and mechanical cues will be needed. The objective of this review is to describe the current state-of-the-art, challenges and future directions in the field of enthesis tissue engineering focusing on four key parameters: (1) scaffold and biomaterials, (2) cells, (3) growth factors and (4) mechanical stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Bone biopsy needles. Mechanical properties, needle design and specimen quality

    International Nuclear Information System (INIS)

    Keulers, Annika; Penzkofer, T.; Cunha-Cruz, V.C.; Bruners, P.; Helmholtz Inst. fuer biomedizinische Technik, Aachen; Braunschweig, T.; Schmitz-Rode, T.; Mahnken, A.; Helmholtz Inst. fuer biomedizinische Technik, Aachen

    2011-01-01

    To quantitatively analyze differences in mechanical properties, needle design including signs of wear, subjective handling and specimen quality of bone biopsy needles. Materials and Methods: In this study 19 different bone biopsy systems (total 38; 2 /type) were examined. With each biopsy needle five consecutive samples were obtained from vertebral bodies of swine. During puncture a force-torques sensor measured the mechanical properties and subjective handling was assessed. Before and after each biopsy the needles were investigated using a profile projector and signs of wear were recorded. Afterwards, a pathologist semi-quantitatively examined the specimen regarding sample quality. The overall evaluation considered mechanical properties, needle wear, subjective handling and sample quality. Differences were assessed for statistical significance using ANOVA and t-test. Results: Needle diameter (p = 0.003) as well as needle design (p = 0.008) affect the mechanical properties significantly. Franseen design is significantly superior to other needle designs. Besides, length reduction recorded by the profile projector, as a quality criterion showed notable distinctions in between the needle designs. Conclusion: Bone biopsy needles vary significantly in performance. Needle design has an important influence on mechanical properties, handling and specimen quality. Detailed knowledge of those parameters would improve selecting the appropriate bone biopsy needle. (orig.)

  13. Experimental study of the radiation effects on the bone growth. Changes in Tc-99m pyrophosphate bone imaging

    International Nuclear Information System (INIS)

    Ohtake, H.; Sakai, Y.; Morita, S.; Kikuchi, S.; Bussaka, Y.; Oshibuchi, M.; Fukae, S.; Kaneyuki, Y.; Umezaki, N.

    1983-01-01

    Bones of immature rabbits during growth period were irradiated and followed up with bone scintigraphy with Tc-99m pyrophosphate. The accumulation ratio of radionuclide was decreased on the irradiated bone from an early period compared to the control side, and the decrease was more pronounced as the dose of irradiation increased. In groups irradiated with less than 4,000 rad, the ratio reached the minimum at 5 weeks, followed by a gradual recovery. These changes were evaluated with reference to the inhibition on longitudinal growth of the bone

  14. The mechanical study of acrylic bone cement reinforced with carbon nanotube

    International Nuclear Information System (INIS)

    Nien, Yu-Hsun; Huang, Chiao-li

    2010-01-01

    Bone cement is used as filler between prosthesis and bone for fixation and force distribution. The major composition of bone cement is polymethylmethacrylate (PMMA). Some disadvantages of PMMA bone cement are found such as significant poor mechanical properties which may cause failure of the cement. In this paper, we exploited carbon nanotube to enhance the mechanical properties of bone cement. The mechanical properties of the bone cement were characterized using tensile and compressive analysis as well as dynamic mechanical analysis (DMA). The result shows that carbon nanotube is able to enhance the mechanical properties of the modified bone cement.

  15. The mechanical study of acrylic bone cement reinforced with carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    Nien, Yu-Hsun, E-mail: nienyh@yuntech.edu.tw [Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin 64002, Taiwan (China); Huang, Chiao-li [Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin 64002, Taiwan (China)

    2010-05-25

    Bone cement is used as filler between prosthesis and bone for fixation and force distribution. The major composition of bone cement is polymethylmethacrylate (PMMA). Some disadvantages of PMMA bone cement are found such as significant poor mechanical properties which may cause failure of the cement. In this paper, we exploited carbon nanotube to enhance the mechanical properties of bone cement. The mechanical properties of the bone cement were characterized using tensile and compressive analysis as well as dynamic mechanical analysis (DMA). The result shows that carbon nanotube is able to enhance the mechanical properties of the modified bone cement.

  16. Bone Mechanical Strength Estimation from Micro X-ray CT Image

    National Research Council Canada - National Science Library

    Matani, A

    2001-01-01

    ... (Bone Mineral Density), an index to evaluate the mechanical strength of the bone, does not always reflect the strength, On the other hand, micro X-ray CT has revealed the inner structure of bone, Under such circumstances...

  17. Normal epidermal growth factor receptor signaling is dispensable for bone anabolic effects of parathyroid hormone.

    Science.gov (United States)

    Schneider, Marlon R; Dahlhoff, Maik; Andrukhova, Olena; Grill, Jessica; Glösmann, Martin; Schüler, Christiane; Weber, Karin; Wolf, Eckhard; Erben, Reinhold G

    2012-01-01

    Although the bone anabolic properties of intermittent parathyroid hormone (PTH) have long been employed in the treatment of osteoporosis, the molecular mechanisms behind this action remain largely unknown. Previous studies showed that PTH increases the expression and the activity of epidermal growth factor receptor (EGFR) in osteoblasts, and activation of ERK1/2 by PTH in osteoblasts was demonstrated to induce the proteolytical release of EGFR ligands and EGFR transactivation. However, conclusive evidence for an important role of the EGFR system in mediating the anabolic actions of intermittent PTH on bone in vivo is lacking. Here, we evaluated the effects of intermittent PTH on bone in Waved-5 (Wa5) mice which carry an antimorphic Egfr allele whose product acts as a dominant negative receptor. Heterozygous Wa5 females and control littermates received a subcutaneous injection of PTH (80 μg/kg) or buffer on 5 days per week for 4 weeks. Wa5 mice had slightly lower total bone mineral density (BMD), but normal cancellous bone volume and turnover in the distal femoral metaphysis. The presence of the antimorphic Egfr allele neither influenced the PTH-induced increase in serum osteocalcin nor the increases in distal femoral BMD, cortical thickness, cancellous bone volume, and cancellous bone formation rate. Similarly, the PTH-induced rise in lumbar vertebral BMD was unchanged in Wa5 relative to wild-type mice. Wa5-derived osteoblasts showed considerably lower basal extracellular signal-regulated kinase 1/2 (ERK1/2) activation as compared to control osteoblasts. Whereas activation of ERK1/2 by the EGFR ligand amphiregulin was largely blocked in Wa5 osteoblasts, treatment with PTH induced ERK1/2 activation comparable to that observed in control osteoblasts, relative to baseline levels. Our data indicate that impairment of EGFR signaling does not affect the anabolic action of intermittent PTH on cancellous and cortical bone. Copyright © 2011. Published by Elsevier Inc.

  18. Mechanical stimulation of bone cells using fluid flow

    NARCIS (Netherlands)

    Huesa, C.; Bakker, A.D.

    2012-01-01

    This chapter describes several methods suitable for mechanically stimulating monolayers of bone cells by fluid shear stress (FSS) in vitro. Fluid flow is generated by pumping culture medium through two parallel plates, one of which contains a monolayer of cells. Methods for measuring nitric oxide

  19. The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect

    Directory of Open Access Journals (Sweden)

    So-Hyoun Lee

    2017-01-01

    Full Text Available The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS- PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR. The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %, the bone-to-implant contact (BIC, %, distance from the new bone to the old bone (NB-OB, %, and distance from the osseointegration to the old bone (OI-OB, % were significantly higher in the 3D-PFTM group than the CM group (p<.001. It was verified that the 3D-PFTM increased mechanical properties which were effective in supporting the space maintenance ability and stabilizing the particulate bone grafts, which led to highly efficient bone regeneration.

  20. Hydroxyapatite-binding peptides for bone growth and inhibition

    Science.gov (United States)

    Bertozzi, Carolyn R [Berkeley, CA; Song, Jie [Shrewsbury, MA; Lee, Seung-Wuk [Walnut Creek, CA

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  1. Detection of fungi colony growth on bones by dynamic speckle

    Science.gov (United States)

    Vincitorio, F. M.; Budini, N.; Mulone, C.; Spector, M.; Freyre, C.; López Díaz, A. J.; Ramil, A.

    2013-11-01

    In this work we have studied the dynamic speckle patterns of mucor fungi colonies, which were inoculated on different samples. We were interested in analyzing the development of fungi colonies in bones, since during the last two years, a series of infections by mucor fungi have been reported on patients from different hospitals in Argentina. Coincidentally, all of these infections appeared on patients that were subjected to a surgical intervention for implantation of a titanium prosthesis. Apparently, the reason of the infection was a deficient sterilization process in conjunction with an accidental contamination. We observed that fungi growth, activity and death can be distinguished by means of the dynamic speckle technique.

  2. Mechanical compression of a fibrous membrane surrounding bone causes bone resorption

    NARCIS (Netherlands)

    van der Vis, H. M.; Aspenberg, P.; Tigchelaar, W.; van Noorden, C. J.

    1999-01-01

    Early micromovement and migration of a prosthesis of a hip or knee predicts late clinical loosening of the prosthesis. Such migration is likely to be associated with mechanical compression of the fibrous membrane interpositioned between bone and prosthesis during movement. Compression of the fibrous

  3. The mathematics and mechanics of biological growth

    CERN Document Server

    Goriely, Alain

    2017-01-01

    This monograph presents a general mechanical theory for biological growth. It provides both a conceptual and a technical foundation for the understanding and analysis of problems arising in biology and physiology. The theory and methods is illustrated on a wide range of examples and applications. A process of extreme complexity, growth plays a fundamental role in many biological processes and is considered to be the hallmark of life itself. Its description has been one of the fundamental problems of life sciences, but until recently, it has not attracted much attention from mathematicians, physicists, and engineers. The author herein presents the first major technical monograph on the problem of growth since D’Arcy Wentworth Thompson’s 1917 book On Growth and Form. The emphasis of the book is on the proper mathematical formulation of growth kinematics and mechanics. Accordingly, the discussion proceeds in order of complexity and the book is divided into five parts. First, a general introduction on the pro...

  4. Concepts on Low Temperature Mechanical Grain Growth

    Energy Technology Data Exchange (ETDEWEB)

    Sharon, John Anthony [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Metallurgy and Materials Joining Dept.; Boyce, Brad Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Metallurgy and Materials Joining Dept.

    2013-11-01

    In metals, as grain size is reduced below 100nm, conventional dislocation plasticity is suppressed resulting in improvements in strength, hardness, and wears resistance. Existing and emerging components use fine grained metals for these beneficial attributes. However, these benefits can be lost in service if the grains undergo growth during the component’s lifespan. While grain growth is traditionally viewed as a purely thermal process that requires elevated temperature exposure, recent evidence shows that some metals, especially those with nanocrystalline grain structure, can undergo grain growth even at room temperature or below due to mechanical loading. This report has been assembled to survey the key concepts regarding how mechanical loads can drive grain coarsening at room temperature and below. Topics outlined include the atomic level mechanisms that facilitate grain growth, grain boundary mobility, and the impact of boundary structure, loading scheme, and temperature.

  5. Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

    DEFF Research Database (Denmark)

    Hyldstrup, L; Conway, G S; Racz, K

    2012-01-01

    Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength....... INTRODUCTION: In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions. METHODS...

  6. Growth in children following irradiation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Bushhouse, S.; Ramsay, N.K.; Pescovitz, O.H.; Kim, T.; Robison, L.L.

    1989-01-01

    Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression

  7. Growth of the flat bones of the membranous neurocranium: a computational model.

    Science.gov (United States)

    Garzón-Alvarado, Diego A; González, Andres; Gutiérrez, Maria Lucia

    2013-12-01

    This article assumes two stages in the formation of the bones in the calvaria, the first one takes into account the formation of the primary centers of ossification. This step counts on the differentiation from mesenchymal cells into osteoblasts. A molecular mechanism is used based on a system of reaction-diffusion between two antagonistic molecules, which are BMP2 and Noggin. To this effect we used equations whose behavior allows finding Turing patterns that determine the location of the primary centers. In the second step of the model we used a molecule that is expressed by osteoblasts, called Dxl5 and that is expressed from the osteoblasts of each flat bone. This molecule allows bone growth through its borders through cell differentiation adjacent to each bone of the skull. The model has been implemented numerically using the finite element method. The results allow us to observe a good approximation of the formation of flat bones of the membranous skull as well as the formation of fontanelles and sutures. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.

    Science.gov (United States)

    Jakus, Adam E; Rutz, Alexandra L; Jordan, Sumanas W; Kannan, Abhishek; Mitchell, Sean M; Yun, Chawon; Koube, Katie D; Yoo, Sung C; Whiteley, Herbert E; Richter, Claus-Peter; Galiano, Robert D; Hsu, Wellington K; Stock, Stuart R; Hsu, Erin L; Shah, Ramille N

    2016-09-28

    Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors. Copyright © 2016, American Association for the Advancement of Science.

  9. Vascularized bone transplant chimerism mediated by vascular endothelial growth factor.

    Science.gov (United States)

    Willems, Wouter F; Larsen, Mikko; Friedrich, Patricia F; Bishop, Allen T

    2015-01-01

    Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells. Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER). At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups. These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient-derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc.

  10. Fatigue crack growth behavior in equine cortical bone

    Science.gov (United States)

    Shelton, Debbie Renee

    2001-07-01

    Objectives for this research were to experimentally determine crack growth rates, da/dN, as a function of alternating stress intensity factor, DeltaK, for specimens from lateral and dorsal regions of equine third metacarpal cortical bone tissue, and to determine if the results were described by the Paris law. In one set of experiments, specimens were oriented for crack propagation in the circumferential direction with the crack plane transverse to the long axis of the bone. In the second set of experiments, specimens were oriented for radial crack growth with the crack plane parallel to the long axis of the bone. Results of fatigue tests from the latter specimens were used to evaluate the hypothesis that crack growth rates differ regionally. The final experiments were designed to determine if crack resistance was dependent on region, proportion of hooped osteons (those with circumferentially oriented collagen fibers in the outer lamellae) or number of osteons penetrated by the crack, and to address the hypothesis that hooped osteons resist invasion by cracks better than other osteonal types. The transverse crack growth data for dorsal specimens were described by the Paris law with an exponent of 10.4 and suggested a threshold stress intensity factor, DeltaKth, of 2.0 MPa·m1/2 and fracture toughness of 4.38 MPa·m 1/2. Similar results were not obtained for lateral specimens because the crack always deviated from the intended path and ran parallel to the loading direction. Crack growth for the dorsal and lateral specimens in the radial orientation was described by the Paris law with exponents of 8.7 and 10.2, respectively, and there were no regional differences in the apparent DeltaK th (0.5 MPa·m1/2) or fracture toughness (1.2 MPa·m 1/2). Crack resistance was not associated with cortical region, proportion of hooped osteons or the number of osteons penetrated by the crack. The extent to which cracks penetrate osteons was influenced by whether the collagen fiber

  11. Experimental study on the radiation effects to the bone growth

    International Nuclear Information System (INIS)

    Sakai, Yasuhiko

    1980-01-01

    The radiation effects on growing bone were studied using immature rabbits. The irradiation was done with telecobalt to the right knee joint. The rabbits were divided into six groups according to the dose, such as 1,000, 2,000, 3,000, 4,000, 6,000 and 8,000 rad respectively. The effects of irradiation were investigated by RI-scintigraphy, X-ray photography and pathohistological examination. The following results were obtained. 1. In RI-scintigraphy using sup(99m)Tc-MDP, the change of accumulation ratio of the irradiated side was investigated. In terms of chronological observation, the accumulation ratio decreased most 5 weeks after irradiation and subsequently increased in the group irradiated with less than 4,000 rad. In the 6,000 rad group, the accumulation ratio decreased rapidly until 5 weeks after irradiation, and subsequently increased slightly. In the 8,000 rad group, the accumulation ratio progressively decreased unabated during the time observed. 2. X-ray findings of irradiated bones were as follows: In the group irradiated with more than 3,000 rad, sclerosis of the metaphysis and unclearness of the trabecula, thickening of the compact bone, bending, fissure and fracture of the bone appeared early with increased frequency with an increased in radiation doses. Also, according to an increase in radiation doses, growth inhibition in the length of the tibia was conspicuous. 3. In the histopathological findings, disturbances of the epiphyseal cartilage, the blood vessel system, trabecula, and medullary tissue becomes intense with increasing radiation doses. (author)

  12. [The concentration of growth factors in patients with inherent and acquired shortenings of limbs bones].

    Science.gov (United States)

    Strogov, M V; Luneva, S N; Novikov, K I

    2013-04-01

    The article deals with the results of study of level of growth factors in blood serum of patients with inherent and post-traumatic shortenings of limbs' bones. The detection in blood serum the level of epidermal growth factor insulin-like growth factor I and angiopoetins is proposed to monitor in given patients the reparative bone formation.

  13. Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

    Science.gov (United States)

    Brouwers, J E M; van Donkelaar, C C; Sengers, B G; Huiskes, R

    2006-01-01

    Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

  14. Mechanisms of diabetes mellitus-induced bone fragility.

    Science.gov (United States)

    Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

    2017-04-01

    The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

  15. Effects of spaceflight and Insulin-like Growth Factor-1 on rat bone properties

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, T.A.; Ayers, R.A.; Spetzler, M.L.; Simske, S.J. [BioServe Space Technologies University of Colorado Boulder, Colorado80309-0429 (United States); Zimmerman, R.J. [Chiron Corporation 4560 Horton Street Emeryville, California94608-2916 (United States)

    1997-01-01

    Spaceflight induces bone degradation which is analogous to an accelerated onset of osteoporosis in humans (Tilton {ital et al.}, 1980). In rats, decreased bone formation is indicative of reduced osteoblast activity (Morey and Baylink, 1978). Chiron Corporation (Emeryville, CA) is interested in using the microgravity environment of low-Earth-orbit to test its therapeutic drug, Insulin-like Growth Factor-1 (IGF-1). This pharmaceutic is known to promote osteoblast activity (Schmid {ital et al.}, 1984) and therefore may encourage bone growth in rats. Chiron sponsored the Immune.3 payload on STS-73 (May 19{endash}29, 1996) through its Center for Space Commercialization (CSC) partner BioServe Space Technologies (University of Colorado and Kansas State University) to investigate the effects of IGF-1 on mitigating the skeletal degradation that affects rats and humans during spaceflight. Twelve rats were flown for 10 days using two Animal Enclosure Modules (AEMs) provided by NASA Ames Research Center. Of the twelve, six received 1.4 mg/day of IGF-1; the other six saline. Sixteen vivarium ground controls received the same treatment on a one day delay. Rat femora and tibiae were examined for bone mineral density via DXA scan. Femora and humeri were measured for physical and compositional properties, as well as mechanically tested in three point flexure. Quantitative histomorphometric examination of tibiae, humeri, fibulae, ribs and cranial bone; and microhardness testing on tibiae and humeri are currently in progress. Flight humeri and vivarium femora were significantly larger than their counterparts; however, significant differences in mechanical properties and mineral density were not concurrent to these mass changes. {copyright} {ital 1997 American Institute of Physics.}

  16. Osteocyte-derived insulin-like growth factor I is not essential for the bone repletion response in mice.

    Directory of Open Access Journals (Sweden)

    Kin-Hing William Lau

    Full Text Available The present study sought to evaluate the functional role of osteocyte-derived IGF-I in the bone repletion process by determining whether deficient expression of Igf1 in osteocytes would impair the bone repletion response to one week of dietary calcium repletion after two weeks of dietary calcium deprivation. As expected, the two-week dietary calcium depletion led to hypocalcemia, secondary hyperparathyroidism, and increases in bone resorption and bone loss in both Igf1 osteocyte conditional knockout (cKO mutants and WT control mice. Thus, conditional disruption of Igf1 in osteocytes did not impair the calcium depletion-induced bone resorption. After one week of calcium repletion, both cKO mutants and WT littermates showed an increase in endosteal bone formation attended by the reduction in osteoclast number, indicating that deficient Igf1 expression in osteocytes also did not have deleterious effects on the bone repletion response. The lack of an effect of deficient osteocyte-derived IGF-I expression on bone repletion is unexpected since previous studies show that these Igf1 osteocyte cKO mice exhibited impaired developmental growth and displayed complete resistance to bone anabolic effects of loading. These studies suggest that there is a dichotomy between the mechanisms necessary for anabolic responses to mechanical loading and the regulatory hormonal and anabolic skeletal repletion following low dietary calcium challenge. In conclusion, to our knowledge this study has demonstrated for the first time that osteocyte-derived IGF-I, which is essential for anabolic bone response to mechanical loading, is not a key regulatory factor for bone repletion after a low calcium challenge.

  17. The Effect of Altering the Mechanical Loading Environment on the Expression of Bone Regenerating Molecules in Cases of Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    Mohammad M Alzahrani

    2014-12-01

    Full Text Available Distraction osteogenesis (DO is a surgical technique where gradual and controlled separation of two bony fragments following an osteotomy leads to the induction of new bone formation in the distracted gap. DO is used for limb lengthening, correction of bony deformities and the replacement of bone loss secondary to infection, trauma and tumors. Although DO gives satisfactory results in most cases, one major drawback of this technique is the prolonged period of time the external fixator has to be kept on until the newly formed bone consolidates thus leading to numerous complications. Numerous attempts at accelerating bone formation during DO have been reported. One specific approach is manipulation of the mechanical environment during DO by applying changes in the standard protocol of distraction. Attempts at changing this mechanical environment led to mixed results. Increasing the rate or applying acute distraction, led to poor bone formation in the distracted zone. On the other hand, the addition of compressive forces (such as weight bearing, alternating distraction with compression or by over-lengthening and then shortening has been reported to increase bone formation. It still remains unclear why these alterations may lead to changes in bone formation. While the cellular and molecular changes occurring during the standard DO protocol, specifically increased expression of transforming growth factor-β1, platelet derived growth factor, insulin-like growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and bone morphogenic proteins have been extensively investigated, the literature is sparse on the changes occurring when this protocol is altered. It is the purpose of this article to review the pertinent literature on the changes in the expression of various proteins and molecules as a result of changes in the mechanical loading technique in DO and try to define potential future research directions.

  18. Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

    Science.gov (United States)

    Torres, Ashley M; Matheny, Jonathan B; Keaveny, Tony M; Taylor, David; Rimnac, Clare M; Hernandez, Christopher J

    2016-03-15

    Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

  19. Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis.

    Science.gov (United States)

    Raisingani, Manish; Preneet, Brar; Kohn, Brenda; Yakar, Shoshana

    2017-06-01

    Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM. Copyright © 2017. Published by Elsevier Ltd.

  20. Mechanisms of bone remodeling: implications for clinical practice.

    Science.gov (United States)

    Kenny, Anne M; Raisz, Lawrence G

    2002-01-01

    The adult skeleton undergoes continuous remodeling. The remodeling cycle involves the interaction of cells of osteoblastic and osteoclastic lineage and is regulated by both systemic hormones and local factors. In addition to the systemic calcium-regulating hormones, parathyroid hormone, 1,25-dihydroxy vitamin D and calcitonin, sex hormones play an important role. Estrogen has been identified as the major inhibitor of bone resorption in both men and women. Androgen is important not only as a source of estrogen, through the action of aromatase, but also for its direct effect in stimulating bone formation. The effects of sex hormones may be mediated by their ability to alter the secretion of local cytokines, prostaglandins and growth factors. Sex hormone action is also modulated by the level of sex hormone-binding globulin in the circulation. A more precise analysis of these effects has been made possible by the development of new methods of measuring not only bone mineral density, but also relative rates of bone formation and resorption using biochemical markers. These new approaches have allowed us to define more precisely the specific roles of androgens, estrogens and other regulatory hormones in human skeletal physiology and pathophysiology.

  1. Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading

    Science.gov (United States)

    Kubota, Takuo; Elalieh, Hashem Z.; Saless, Neema; Fong, Chak; Wang, Yongmei; Babey, Muriel; Cheng, Zhiqiang; Bikle, Daniel D.

    2013-11-01

    Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor-1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/-) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.

  2. The consequences of pediatric renal transplantation on bone metabolism and growth.

    Science.gov (United States)

    Bacchetta, Justine; Ranchin, Bruno; Demède, Delphine; Allard, Lise

    2013-10-01

    During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

  3. Mechanics of quasi-static crack growth

    Energy Technology Data Exchange (ETDEWEB)

    Rice, J R

    1978-10-01

    Results on the mechanics of quasi-static crack growth are reviewed. These include recent studies on the geometry and stability of crack paths in elastic-brittle solids, and on the thermodynamics of Griffith cracking, including environmental effects. The relation of crack growth criteria to non-elastic rheological models is considered and paradoxes with energy balance approaches, based on singular crack models, are discussed for visco-elastic, diffuso-elastic, and elastic-plastic materials. Also, recent approaches to prediction of stable crack growth in ductile, elastic-plastic solids are discussed.

  4. The in vitro viability and growth of fibroblasts cultured in the presence of different bone grafting materials (NanoBone and Straumann Bone Ceramic).

    Science.gov (United States)

    Kauschke, E; Rumpel, E; Fanghänel, J; Bayerlein, T; Gedrange, T; Proff, P

    2006-02-01

    Different clinical applications, including dentistry, are making increasing demands on bone grafting material. In the present study we have analysed the viability, proliferation and growth characteristics of fibroblasts cultured in vitro together with two different bone grafting materials, NanoBone and Straumann Bone Ceramic, over a period of 24 and 28 days respectively. Viability was measured at least every 72 hours by using the alamarBlue assay, a test that measures quantitatively cell proliferation and viability but does not require cell fixation or extraction. After one week of culture fibroblast viability was as high as in controls for both grafting materials and remained high (> 90%) for the duration of the experiment. Cell growth was evaluated microscopically. Scanning electron microscopy revealed a dense fibroblast growth at the surface of both bone grafting materials after three weeks of in vitro culture. Generally, our in vitro analyses contribute to further insights into cell - scaffold interactions.

  5. Parameters affecting mechanical and thermal responses in bone drilling: A review.

    Science.gov (United States)

    Lee, JuEun; Chavez, Craig L; Park, Joorok

    2018-04-11

    Surgical bone drilling is performed variously to correct bone fractures, install prosthetics, or for therapeutic treatment. The primary concern in bone drilling is to extract donor bone sections and create receiving holes without damaging the bone tissue either mechanically or thermally. We review current results from experimental and theoretical studies to investigate the parameters related to such effects. This leads to a comprehensive understanding of the mechanical and thermal aspects of bone drilling to reduce their unwanted complications. This review examines the important bone-drilling parameters of bone structure, drill-bit geometry, operating conditions, and material evacuation, and considers the current techniques used in bone drilling. We then analyze the associated mechanical and thermal effects and their contributions to bone-drilling performance. In this review, we identify a favorable range for each parameter to reduce unwanted complications due to mechanical or thermal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Mechanisms of radiation induced creep and growth

    International Nuclear Information System (INIS)

    Bullough, R.; Wood, M.H.

    1980-01-01

    Irradiation creep occurs primarily because the applied stress causes the evolving microstructure to respond in an anisotropic fashion to the interstitial and vacancy fluxes. On the other hand, irradiation growth requires the response to be naturally anisotropic in the absence of applied stress. Four fundamental mechanisms of irradiation creep have been conjectured: stress induced preferred absorption (SIPA) of the point defects on the dislocations, stress induced preferred nucleation (SIPN) of point defects in planar aggregates (edge dislocation loops), stress induced climb and glide (SICG) of the dislocation network and stress induced gas driven interstitial deposition (SIGD). These mechanisms will be briefly outlined and commented upon. The contributions made by these mechanisms to the total strain are not, in general, mutually separable and also depend on the prevailing (and changing) microstructure during irradiation. The fundamental mechanism of irradiation growth will be discussed: it is believed to arise by the preferred condensation of point defects and climb of dislocation loops and network on certain crystallographic planes. The preferred absorption and nucleation is thus a consequence of natural crystallographic anisotropy and not due to any external stresses. Again the effectiveness of this mechanism depends on the prevailing microstructure in the material. In this connection will be particularly drawn to the significance of solute trapping, segregation at grain boundaries, dislocation bias for interstitials and transport parameters for an understanding of irradiation growth in materials like zirconium and its alloys; the relevance of recent simulation studies of growth in such materials using electrons to the growth under neutron irradiation will be discussed in detail and a consistent model of growth in these materials will be presented. (orig.)

  7. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of f...

  8. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  9. Parental bone marrow growth in young hybrid mice

    International Nuclear Information System (INIS)

    Chervenak, R.P.

    1979-01-01

    When bone marrow is transplated from certain inbred mouse strains to F 1 hybrids of that strain, the graft often fails to proliferate. It has been reported that this phenomenon, known as Poor Growth, is not demonstrable in recipients less than three weeks of age. The purpose of the present study was to investigate some of the parameters involved in this phenomenon and its sudden appearance at three weeks of age. By employing 125 IUdR uptake and hemopoietic colony assays following transplantation of marrow to mice of various ages and treatment groups, the following conclusions were drawn. (1) Parental marrow grew equally well in both parental strain and F 1 hybrid recipients less than three weeks old; (2) The observed growth of hemopoietic tissue was not due to endogeneous stem cell proliferation; (3) Changes in radiation sensitivity did not account for the fluctuations of hemopoiesis seen in mice from one to five weeks of age; (4) Neither stimulator cells in mice less than three weeks of age nor graft destroying cells in older mice could be demonstrated. Two mechanistic models of Poor Growth are presented and discussed and a new model is proposed

  10. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease.

    Science.gov (United States)

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Mechanical properties of a biodegradable bone regeneration scaffold

    Science.gov (United States)

    Porter, B. D.; Oldham, J. B.; He, S. L.; Zobitz, M. E.; Payne, R. G.; An, K. N.; Currier, B. L.; Mikos, A. G.; Yaszemski, M. J.

    2000-01-01

    Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

  12. The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth

    International Nuclear Information System (INIS)

    Oestreich, Alan E.

    2004-01-01

    In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle. (orig.)

  13. The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth

    Energy Technology Data Exchange (ETDEWEB)

    Oestreich, Alan E. [Department of Radiology, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, OH 45229-3039, Cincinnati (United States)

    2004-03-01

    In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle. (orig.)

  14. Mechanical mandible competence in rats with nutritional growth retardation.

    Science.gov (United States)

    Lezón, Christian Esteban; Pintos, Patricia Mabel; Bozzini, Clarisa; Romero, Alan Agüero; Casavalle, Patricia; Friedman, Silvia María; Boyer, Patricia Mónica

    2017-08-01

    In order to provide a better understanding of the sympathetic nervous system as a negative regulator of bone status, the aim of the study was to establish the biomechanical mandible response to different doses of a β-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. Rats were assigned to eight groups: Control (C), C+P3.5 (CP3.5), C+P7 (CP7), C+P14 (CP14), NGR, NGR+P3.5 (NGRP3.5), NGR+P7 (NGRP7) and NGR+P14 (NGRP14). C, CP3.5, CP7 and CP14 rats were freely fed with the standard diet. NGR, NGRP3.5, NGRP7 and NGRP14 rats received, for 4 weeks (W4), 80% of the amount of controls food consumed. Propranolol 3.5, 7 and 14mg/kg/day was injected ip 5days per week in CP3.5 and NGRP3.5, CP7 and NGRP7, CP14 and NGRP14, respectively. At W4, zoometry, mandible morphometry, static histomorphometric and biomechanical competence were performed. A dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. These findings evidenced that sympathetic nervous system activity is a negative regulator of mandible mechanical competence in the nutritional growth retardation model. Propranolol 7mg/kg/day, under the regimen usage, seems to be appropriate to blockade SNS activity on mandible mechanical performance in NGR rats, probably associated to an effect on bone mechanostat system ability to detect disuse mode as an error. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Skeletal development of mice lacking bone sialoprotein (BSP--impairment of long bone growth and progressive establishment of high trabecular bone mass.

    Directory of Open Access Journals (Sweden)

    Wafa Bouleftour

    Full Text Available Adult Ibsp-knockout mice (BSP-/- display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice

  16. Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling.

    Science.gov (United States)

    Farquharson, Colin; Ahmed, S Faisal

    2013-04-01

    Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.

  17. Mechanical Properties of 3d Scaffolds for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Deividas Mizeras

    2017-01-01

    Full Text Available One of the biggest challenges in modern tissue engineering is a creation 3D scaffolds for bone tissue regeneration. Until now, in order to restore bone defects are used various bone substitutes (autologous and allogeneic, however, their usage is limited because is required additional surgery, possible complications, also limited their use is associated with ethical point of view. In this work we aim to determine the mechanical properties of 3D printed PLA objects having various orientation woodpile microarchitectures. In this work we chose three different 3D microarchitectures: woodpile BCC (each layer consists of parallel logs which are rotated 90 deg every next layer, woodpile FCC (every layer is additionally shifted half of the period in respect to the previous parallel log layer and a rotating woodpile 60 deg (each layer is rotated 60 deg in respect to the previous one. Compressive and bending tests were carried out with TIRAtest2300 universal testing machine. We found that 60 deg rotating woodpile geometry had the highest mechanical values which were approximately about 3 times higher than the BCC or FCC microstructures.

  18. A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

    Science.gov (United States)

    Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

    2016-11-01

    The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue

  19. Bone growth during rapamycin therapy in young rats

    Directory of Open Access Journals (Sweden)

    He Yu-Zhu

    2009-01-01

    significantly decreased endochondral bone growth. No catch-up growth was demonstrated at the end of 4 weeks, although markers of chondrocyte proliferation and differentiation improved. Clinical studies need to be done to evaluate these changes in growing children.

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  3. Mixed reality temporal bone surgical dissector: mechanical design.

    Science.gov (United States)

    Hochman, Jordan Brent; Sepehri, Nariman; Rampersad, Vivek; Kraut, Jay; Khazraee, Milad; Pisa, Justyn; Unger, Bertram

    2014-08-08

    The Development of a Novel Mixed Reality (MR) Simulation. An evolving training environment emphasizes the importance of simulation. Current haptic temporal bone simulators have difficulty representing realistic contact forces and while 3D printed models convincingly represent vibrational properties of bone, they cannot reproduce soft tissue. This paper introduces a mixed reality model, where the effective elements of both simulations are combined; haptic rendering of soft tissue directly interacts with a printed bone model. This paper addresses one aspect in a series of challenges, specifically the mechanical merger of a haptic device with an otic drill. This further necessitates gravity cancelation of the work assembly gripper mechanism. In this system, the haptic end-effector is replaced by a high-speed drill and the virtual contact forces need to be repositioned to the drill tip from the mid wand. Previous publications detail generation of both the requisite printed and haptic simulations. Custom software was developed to reposition the haptic interaction point to the drill tip. A custom fitting, to hold the otic drill, was developed and its weight was offset using the haptic device. The robustness of the system to disturbances and its stable performance during drilling were tested. The experiments were performed on a mixed reality model consisting of two drillable rapid-prototyped layers separated by a free-space. Within the free-space, a linear virtual force model is applied to simulate drill contact with soft tissue. Testing illustrated the effectiveness of gravity cancellation. Additionally, the system exhibited excellent performance given random inputs and during the drill's passage between real and virtual components of the model. No issues with registration at model boundaries were encountered. These tests provide a proof of concept for the initial stages in the development of a novel mixed-reality temporal bone simulator.

  4. A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth

    Directory of Open Access Journals (Sweden)

    Benedetta Gualeni

    2013-11-01

    Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.

  5. Effects of Antiseptic Solutions Commonly Used in Dentistry on Bone Viability, Bone Morphology, and Release of Growth Factors.

    Science.gov (United States)

    Sawada, Kosaku; Fujioka-Kobayashi, Masako; Kobayashi, Eizaburo; Schaller, Benoit; Miron, Richard J

    2016-02-01

    Antiseptic solutions are commonly used in dentistry for a number of sterilization procedures, including harvesting of bone chips, irrigation of extraction sockets, and sterilization of osteonecrotic bone. Despite its widespread use, little information is available regarding the effects of various antiseptic solutions on bone cell viability, morphology, and the release of growth factors. The antiseptic solutions included 1) 0.5% povidone iodine (PI), 2) 0.2% chlorhexidine diguluconate (CHX), 3) 1% hydrogen peroxide (H2O2), and 4) 0.25% sodium hypochlorite (HYP). Bone samples collected from porcine mandibular cortical bone were rinsed in the antiseptic solutions for 10 minutes and assessed for cell viability using an MTS assay and protein release of transforming growth factor (TGF-β1), bone morphogenetic protein 2 (BMP2), vascular endothelial growth factor (VEGF), interleukin (IL)-1β, and receptor activator of nuclear factor κB ligand (RANKL) using an enzyme-linked immunosorbent assay at 15 minutes and 4 hours after rinsing. After antiseptic rinsing, changes to the surface protein content showed marked alterations, with an abundant protein layer remaining on CHX-rinsed bone samples. The amount of surface protein content gradually decreased in the following order: CHX, H2O2, PI, and HYP. A similar trend was also observed for the relative cell viability from within bone samples after rinsing, with up to 6 times more viable cells found in the CHX-rinsed bone samples than in the HYP- and PI-rinsed samples. An analysis of the growth factors found that both HYP and PI had significantly lower VEGF and TGF-β1 protein release from bone samples at 15 minutes and 4 hours after rinsing compared with CHX and H2O2. A similar trend was observed for RANKL and IL-1β protein release, although no change was observed for BMP2. The results from the present study have demonstrated that antiseptic solutions present with very different effects on bone samples after 10 minutes of

  6. Effect of parathyroidectomy on bone growth and composition in the young rat

    Science.gov (United States)

    Keil, L. C.; Prinz, J. A.; Evans, J. W.

    1974-01-01

    In an effort to determine the influence of the parathyroids on bone growth and composition, 28-day-old male Sprague-Dawley rats were sacrificed 28, 56, and 84 days after parathyroidectomy or sham parathyroidectomy. Body growth as well as femur growth were retarded following parathyroidectomy. Hypocalcemia and hyperphosphatemia occurred in all parathyroidectomized rats; no alterations in plasma magnesium levels were noted. Femur magnesium was increased by 22-30% in the parathyroidectomized rats whereas femur calcium remained unchanged. Bone phosphorus was increased 56 and 84 days following parathyroidectomy. Results of this study indicate that parathyroidectomy retards growth while increasing bone magnesium and phosphorus content.

  7. Peri-Implant Crestal Bone Loss: A Putative Mechanism

    Directory of Open Access Journals (Sweden)

    Yuko Ujiie

    2012-01-01

    Full Text Available Purpose. The immunological mechanisms of peri-implant crestal bone loss have, hitherto, not been elucidated. We hypothesized that bacterial products from the microgap cause upregulation of cytokines in otherwise healthy peri-implant cells, which results in osteoclast formation and, ultimately, in bone resorption. Materials and Methods. We used RT-PCR and ELISA to assay mediators of osteoclastogenesis in rat and human macrophages (r-and hMO; bone marrow derived stromal cells (r-and hBMCs; and human gingival fibroblasts (hGF—with or without stimulation by LPS. TRAP positive multinucleate cells were assessed for their resorptive ability. Results. We show that IL-1α, IL-1β, and IL-6 were expressed by all examined cell types, and TNF-α was upregulated in hGF. Secretion of IL-1α and IL-1β proteins was stimulated in hMO by LPS, and IL-6 protein secretion was highly stimulated in hBMCs and hGF. Both LPS and RANKL stimulated macrophages to form osteoclast-like TRAP positive cells, which resorbed calcium phosphate substrates. Conclusion. Taken together, the results of our study support the hypothesis that bacterial endotoxins upregulate enhanced mediators of osteoclastogenesis in resident cells found in the healthy peri-implant compartment and that the local synergistic action of cytokines secreted by such cells results in the genesis of resorptively active osteoclasts.

  8. Nanoparticulate fillers improve the mechanical strength of bone cement.

    Science.gov (United States)

    Gomoll, Andreas H; Fitz, Wolfgang; Scott, Richard D; Thornhill, Thomas S; Bellare, Anuj

    2008-06-01

    Polymethylmethacrylate (PMMA-) based bone cement contains micrometer-size barium sulfate or zirconium oxide particles to radiopacify the cement for radiographic monitoring during follow-up. Considerable effort has been expended to improve the mechanical qualities of cements, largely through substitution of PMMA with new chemical structures. The introduction of these materials into clinical practice has been complicated by concerns over the unknown long-term risk profile of these new structures in vivo. We investigated a new composite with the well characterized chemical composition of current cements, but with nanoparticles instead of the conventional, micrometer-size barium sulfate radiopacifier. In this study, we replaced the barium sulfate microparticles that are usually present in commercial PMMA cements with barium sulfate nanoparticles. The resultant "microcomposite" and "nanocomposite" cements were then characterized through morphological investigations such as ultra-small angle X-ray scattering (USAXS) and scanning electron microscopy (SEM). Mechanical characterization included compression, tensile, compact tension, and fatigue testing. SEM and USAXS showed excellent dispersion of nanoparticles. Substitution of nanoparticles for microparticles resulted in a 41% increase in tensile strain-to-failure (p = 0.002) and a 70% increase in tensile work-of-fracture (p = 0.005). The nanocomposite cement also showed a two-fold increase in fatigue life compared to the conventional, microcomposite cement. In summary, nanoparticulate substitution of radiopacifiers substantially improved the in vitro mechanical properties of PMMA bone cement without changing the known chemical composition.

  9. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1.

    Science.gov (United States)

    Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin

    2015-11-01

    Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. A clinical study evaluating bone mineral mass in the radius during skeletal growth

    International Nuclear Information System (INIS)

    Hagino, Hiroshi

    1989-01-01

    Using 125-I single photon absorptiometry, bone mineral measurements were performed on 206 healthy Japanese children (2 to 19 years of age). Bone mineral content (BMC), bone width (BW) and BMC/BW values were determined for the radius at distal 1/6 site (metaphysis) and distal 1/3 site (diaphysis). BMC/BW values at both sites correlated well with body height and weight. Bone mass in the diaphysis (distal 1/3 site) increased linearly during the 2-19 years of skeletal growth, but bone mass in the metaphysis (1/6 site) increased steeply during the pubertal period. In children receiving glucocorticoid therapy, bone mass was reduced in proportion to the duration of drug administration. In children under anticonvulsant therapy, the yearly increse in bone mass was significantly low especially in those patients with poor physical activity levels. Bone mineral decrease in the radius occurred in the children with hypopituitalism, hypothyroidism (cretinism), hyperthyroidism and Turner's syndrome. (author)

  11. Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.

    Directory of Open Access Journals (Sweden)

    Louise H W Kung

    Full Text Available Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED and pseudoachondroplasia (PSACH. The majority of these diseases feature classical endoplasmic reticulum (ER stress and activation of the unfolded protein response (UPR as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.

  12. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength

    DEFF Research Database (Denmark)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X......-ray absorptiometry (DEXA), compression testing, ashing, and bone histomorphometry were performed. Individuals with CAA had significantly lower bone mineral density (BMD) in the femoral neck and significantly lower bone volume demonstrated by thinner trabeculae, decreased extent of osteoid surfaces, and lower mean...... wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. Conclusion: CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone...

  13. Mechanical properties of human bone-tendon-bone grafts preserved by different methods and radiation sterilised

    International Nuclear Information System (INIS)

    Kaminski, A.; Gut, G.

    2008-01-01

    Full text: Patellar tendon auto and allografts are commonly used in orthopaedic surgery for reconstruction of the anterior crucial ligaments (ACL). Autografts are mainly used for primary reconstruction, while allografts are useful for revision surgery. To avoid the risk of infection diseases transmission allografts should be radiation-sterilised. As radiation-sterilisation is supposed to decrease the mechanical strength of tendon tissue, it is important to establish methods of allografts preservation and sterilisation resulting in their best quality and safety. Therefore, the purpose of the study was to compare the tensile strength of the central one third of human patellar tendon (as used for ACL reconstruction), preserved by different methods (deep fresh freezing, lyophilisation) and subsequently radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. Bone-tendon-bone grafts were prepared from cadaveric human patella tendon with both patellar and tibial attachments. BTB grafts were preserved by deep freezing, glicerolisation or lyophilisation and radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. To estimate mechanical properties all samples were subjected to tensile tests to failure using Instron system. Before these tests all lyophilised grafts were rehydrated. We found decrease of tensile strength of irradiated grafts compared to non-irradiated controls. Obtained results of the mechanical testing of studied grafts indicate their potential usefulness for clinical applications.(Author)

  14. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    International Nuclear Information System (INIS)

    Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

    2013-01-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

  15. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    Science.gov (United States)

    Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

    2013-11-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

  16. Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

    Directory of Open Access Journals (Sweden)

    Jodi A. Carlson Scholz

    2012-12-01

    Full Text Available Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH. Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

  17. Mechanical growth and morphogenesis of seashells

    KAUST Repository

    Moulton, D.E.

    2012-10-01

    Seashells grow through the local deposition of mass along the aperture. Many mathematical descriptions of the shapes of shells have been provided over the years, and the basic logarithmic coiling seen in mollusks can be simulated with few parameters. However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell growth based entirely on the local geometry and mechanics of the aperture and mantle. This local description enables us to efficiently describe both arbitrary growth velocities and the evolution of the shell aperture itself. We demonstrate how most shells can be simulated within this framework. We then turn to the mechanics underlying the shell morphogenesis, and develop models for the evolution of the aperture. We demonstrate that the elastic response of the mantle during shell deposition provides a natural mechanism for the formation of three-dimensional ornamentation in shells. © 2012 Elsevier Ltd.

  18. The role of estrogen in bone growth and formation: changes at puberty

    Directory of Open Access Journals (Sweden)

    Divya Singh

    2010-12-01

    Full Text Available Divya Singh1, Sabyasachi Sanyal2, Naibedya Chattopadhyay11Division of Endocrinology, 2Division of Drug Target Discovery and Development, Central Drug Research Institute (Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, IndiaAbstract: A high peak bone mass (PBM at skeletal maturity is a good predictor for lower rate of fracture risks in later life. Growth during puberty contributes significantly to PBM achievement in women and men. The growth hormone (GH/insulin-like growth factor 1 (IGF-1 axis has a critical role in pubertal bone growth. There is an increase in GH and IGF-1 levels during puberty; thus, it is assumed that sex steroids contribute to higher GH/IGF-1 action during growth. Recent studies indicate that estrogen increases GH secretion in boys and girls, and the major effect of testosterone on GH secretion is via aromatization to estrogen. Estrogen is pivotal for epiphyseal fusion in young men and women. From studies of individuals with a mutated aromatase gene and a case study of male patient with defective estrogen receptor-alpha (ER-α, it is clear that estrogen is indispensable for normal pubertal growth and growth plate fusion. ER-α and estrogen receptor-beta (ER-β have been localized in growth plate and bone. ER knockout studies have shown that ER-α-/- female mice have reduced linear appendicular growth, while ER-β-/- mice have increased appendicular growth. No such effect is seen in ER-β-/- males; however, repressed growth is seen in ER-α-/- males, resulting in shorter long bones. Thus, ER-β represses longitudinal bone growth in female mice, while it has no function in the regulation of longitudinal bone growth in male mice. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.Keywords: peak bone mass, puberty, estrogen, growth plate

  19. Effect of vitamin K2 and growth hormone on the long bones in hypophysectomized young rats: a bone histomorphometry study.

    Science.gov (United States)

    Iwamoto, Jun; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

    2007-01-01

    The purpose of the present study was to determine whether vitamin K(2) and growth hormone (GH) had an additive effect on the long bones in hypophysectomized young rats. Forty-eight female Sprague-Dawley rats (6 weeks old) were assigned to the following five groups by the stratified weight randomization method: intact controls, hypophysectomy (HX) alone, HX + vitamin K(2) (30 mg/kg, p.o., daily), HX + GH (0.625 mg/kg, s.c., 5 days a week), and HX + vitamin K(2) + GH. The duration of the experiment was 4 weeks. HX resulted in a reduction of the cancellous bone volume/total tissue volume (BV/TV) at the proximal tibial metaphysis, as well as decreasing the total tissue area and cortical area of the tibial diaphysis. These changes resulted from a decrease of the longitudinal growth rate and the bone formation rate (BFR)/TV of cancellous bone, as well as a decrease of the periosteal BFR/bone surface (BS) and an increase of endocortical bone turnover (indicated by the BFR/BS) in cortical bone. Administration of vitamin K(2) to HX rats did not affect the cancellous BV/TV or the cortical area. On the other hand, GH completely prevented the decrease of total tissue area and cortical area in cortical bone, as well as the decrease of marrow area and endocortical circumference, by increasing the periosteal BFR/BS compared with that in intact controls and reversing the increase of endocortical bone turnover (BFR/BS). However, GH only partly improved the reduction of the cancellous BV/TV, despite an increase of the longitudinal growth rate and BFR/TV compared with those of intact controls. When administered with GH, vitamin K(2) counteracted the reduction of endocortical bone turnover (BFR/BS) and circumference caused by GH treatment, resulting in no significant difference of marrow area from that in untreated HX rats. These results suggest that, despite the lack of an obvious effect on bone parameters, vitamin K(2) normalizes the size of the marrow cavity during development of

  20. Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

    Science.gov (United States)

    Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

    2012-03-01

    Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth

  1. Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats

    DEFF Research Database (Denmark)

    Lange, Martin; Qvortrup, Klaus; Svendsen, Ole Lander

    2004-01-01

    collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10...

  2. Multidisciplinary characterization of the long-bone cortex growth patterns through sheep's ontogeny.

    Science.gov (United States)

    Cambra-Moo, Oscar; Nacarino-Meneses, Carmen; Díaz-Güemes, Idoia; Enciso, Silvia; García Gil, Orosia; Llorente Rodríguez, Laura; Rodríguez Barbero, Miguel Ángel; de Aza, Antonio H; González Martín, Armando

    2015-07-01

    Bone researches have studied extant and extinct taxa extensively trying to disclose a complete view of the complex structural and chemical transformations that model and remodel the macro and microstructure of bone during growth. However, to approach bone growth variations is not an easy task, and many aspects related with histological transformations during ontogeny remain unresolved. In the present study, we conduct a holistic approach using different techniques (polarized microscopy, Raman spectroscopy and X-ray diffraction) to examine the histomorphological and histochemical variations in the cortical bone of sheep specimens from intrauterine to adult stages, using environmentally controlled specimens from the same species. Our results suggest that during sheep bone development, the most important morphological (shape and size) and chemical transformations in the cortical bone occur during the first weeks of life; synchronized but dissimilar variations are established in the forelimb and hind limb cortical bone; and the patterns of bone tissue maturation in both extremities are differentiated in the adult stage. All of these results indicate that standardized histological models are useful not only for evaluating many aspects of normal bone growth but also to understand other important influences on the bones, such as pathologies that remain unknown. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Growth Mechanism of Nanowires: Ternary Chalcogenides

    Science.gov (United States)

    Singh, N. B.; Coriell, S. R.; Hopkins, R. H.; Su, Ching Hua; Arnold, B.; Choa, Fow-Sen; Cullum, Brian

    2016-01-01

    In the past two decades there has been a large rise in the investment and expectations for nanotechnology use. Almost every area of research has projected improvements in sensors, or even a promise for the emergence of some novel device technologies. For these applications major focuses of research are in the areas of nanoparticles and graphene. Although there are some near term applications with nanowires in photodetectors and other low light detectors, there are few papers on the growth mechanism and fabrication of nanowire-based devices. Semiconductor nanowires exhibit very favorable and promising optical properties, including high transparency and a several order of magnitude better photocurrent than thin film and bulk materials. We present here an overview of the mechanism of nanowire growth from the melt, and some preliminary results for the thallium arsenic selenide material system. Thallium arsenic selenide (TAS) is a multifunctional material combining excellent acousto-optical, nonlinear and radiation detection properties. We observed that small units of (TAS) nanocubes arrange and rearrange at moderate melt undercooling to form the building block of a nanowire. In some cases very long wires (less than mm) are formed. Since we avoided the catalyst, we observed self-nucleation and uncontrolled growth of wires from different places.

  5. Molecular mechanisms of intrauterine growth restriction.

    Science.gov (United States)

    Gurugubelli Krishna, Rao; Vishnu Bhat, B

    2017-07-10

    Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

  6. Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

    Directory of Open Access Journals (Sweden)

    Yusuke Uto

    Full Text Available Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD, Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively, as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution

  7. Effects of porcine somatotropin and dietary phosphorus on growth performance and bone properties of gilts.

    Science.gov (United States)

    Weeden, T L; Nelssen, J L; Goodband, R D; Hansen, J A; Fitzner, G E; Friesen, K G; Laurin, J L

    1993-10-01

    One hundred eight gilts (initial weight = 58.5 kg) were used to determine the effects of porcine somatotropin (pST) and dietary P on growth performance and bone mechanical properties and mineralization during the finishing phase (58 to 105 kg) and a 35-d postfinishing phase. Gilts were injected daily with placebo (control) or 4 mg of pST and fed diets containing .4, .8, or 1.2% P in a 2 x 3 factorial arrangement. From 58 to 105 kg, administration of pST increased (P properties and bone ash. A pST x P interaction was observed (P < .05) for rib bending moment and modulus of elasticity; maximum rib bending moment was attained by control gilts at .8% P and rib modulus of elasticity values remained constant across P levels, whereas rib bending moment and modulus of elasticity increased as dietary P increased from .4 to 1.2% in pST-treated gilts. Administration of pST decreased (P < .05) stress of the rib, femur, and metacarpals compared with control gilts. Increasing dietary P resulted in a linear (P < .10) increase in bending moment, stress, and ash content for rib, femur, and metacarpal bones. The remaining 54 gilts were individually fed 1.8 kg/d of a common diet for 35 d postfinishing.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment......, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  9. The effect of polyunsaturated fatty acids and vitamin D on growth and bone mineralization in children

    DEFF Research Database (Denmark)

    Pedersen, Louise

    2012-01-01

    Polyunsaturated fatty acids (PUFA) and vitamin D are important for fat and bone metabolism but the intake is declining in Western societies with a potential deleterious effect on growth and bone health. Dietary PUFA composition favors the intake of omega-6 (n-6 PUFA) compared to omega-3 (n-3 PUFA...... early in life is essential for preventive steps against development of overweight and obesity. Vitamin D promotes bone mineralization and growth through regulation of the calcium homeostasis, and via activation of vitamin D receptors on bone and cartilage forming cells. However vitamin D insufficiency...... development, and fat percentage; serum vitamin D status in cord blood and height development and bone mineralization; and serum vitamin D status at 4 years and bone mineralization. This is performed in the Copenhagen Prospective Study of Asthma in Childhood (COPSAC2000). In Study 1, breast-milk n-3 PUFA...

  10. Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.

    Science.gov (United States)

    Bredella, Miriam A; Gerweck, Anu V; Barber, Lauren A; Breggia, Anne; Rosen, Clifford J; Torriani, Martin; Miller, Karen K

    2014-05-01

    Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (pbone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may

  11. Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

    Science.gov (United States)

    Troib, Ariel; Guterman, Mayan; Rabkin, Ralph; Landau, Daniel; Segev, Yael

    2016-08-01

    Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

    Science.gov (United States)

    Saurez-Gonzalez, Darilis

    The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was

  13. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration

    OpenAIRE

    Paknejad, M.; Shayesteh, Y. Soleymani; Yaghobee, S.; Shariat, S.; Dehghan, M.; Motahari, P.

    2012-01-01

    Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Materials and Methods: Twelve New Zea...

  14. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration

    OpenAIRE

    M. Paknejad; Y. Soleymani Shayesteh; S. Yaghobee; S. Shariat; M. Dehghan; P. Motahari

    2012-01-01

    Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influ-ence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Materials and Methods: Twelve New Ze...

  15. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    Science.gov (United States)

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  16. Biocompatibility of calcium phosphate bone cement with optimized mechanical properties.

    Science.gov (United States)

    Palmer, Iwan; Nelson, John; Schatton, Wolfgang; Dunne, Nicholas J; Buchanan, Fraser J; Clarke, Susan A

    2016-02-01

    The broad aim of this work was to investigate and optimize the properties of calcium phosphate bone cements (CPCs) for use in vertebroplasty to achieve effective primary fixation of spinal fractures. The incorporation of collagen, both bovine and from a marine sponge (Chondrosia reniformis), into a CPC was investigated. The biological properties of the CPC and collagen-CPC composites were assessed in vitro through the use of human bone marrow stromal cells. Cytotoxicity, proliferation, and osteoblastic differentiation were evaluated using lactate dehydrogenase, PicoGreen, and alkaline phosphatase activity assays, respectively. The addition of both types of collagen resulted in an increase in cytotoxicity, albeit not to a clinically relevant level. Cellular proliferation after 1, 7, and 14 days was unchanged. The osteogenic potential of the CPC was reduced through the addition of bovine collagen but remained unchanged in the case of the marine collagen. These findings, coupled with previous work showing that incorporation of marine collagen in this way can improve the physical properties of CPCs, suggest that such a composite may offer an alternative to CPCs in applications where low setting times and higher mechanical stability are important. © 2015 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

  17. Wnt/RANKL-mediated bone growth promoting effects of blueberries in weanling rats

    Science.gov (United States)

    We studied the effects of dietary blueberry supplementation on bone growth in weanling rats. Weanling male and female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder for 14 and 30 days beginning on PND 21. In both sexes tibial bone mineral density and content a...

  18. Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

    DEFF Research Database (Denmark)

    Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

    2006-01-01

    OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium...

  19. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

    Science.gov (United States)

    Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

    2002-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

  20. Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate Bone Cement on Mechanical Properties and Bioactivity.

    Directory of Open Access Journals (Sweden)

    Tao Li

    Full Text Available This research investigated the mechanical properties and bioactivity of polymethylmethacrylate (PMMA bone cement after addition of the nano-hydroxyapatite(HA coated bone collagen (mineralized collagen, MC.The MC in different proportions were added to the PMMA bone cement to detect the compressive strength, compression modulus, coagulation properties and biosafety. The MC-PMMA was embedded into rabbits and co-cultured with MG 63 cells to exam bone tissue compatibility and gene expression of osteogenesis.15.0%(wt impregnated MC-PMMA significantly lowered compressive modulus while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe and indicated excellent bone tissue compatibility. The bone-cement interface crosslinking was significantly higher in MC-PMMA than control after 6 months implantation in the femur of rabbits. The genes of osteogenesis exhibited significantly higher expression level in MC-PMMA.MC-PMMA presented perfect mechanical properties, good biosafety and excellent biocompatibility with bone tissues, which has profoundly clinical values.

  1. Micro-distribution of uranium in bone after contamination: new insight into its mechanism of accumulation into bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeois, Damien [ICSM, LHYS, Bagnols-sur-Ceze (France); Burt-Pichat, Brigitte [INSERM, UMR 1033 Lyon (France); Lyon Univ. (France); Le Goff, Xavier [ICSM, L2ME, Bagnols-sur-Ceze (France)

    2015-09-15

    After internal contamination, uranium rapidly distributes in the body; up to 20 % of the initial dose is retained in the skeleton, where it remains for years. Several studies suggest that uranium has a deleterious effect on the bone cell system, but little is known regarding the mechanisms leading to accumulation of uranium in bone tissue. We have performed synchrotron radiation-based micro-X-ray fluorescence (SR μ-XRF) studies to assess the initial distribution of uranium within cortical and trabecular bones in contaminated rats' femurs at the micrometer scale. This sensitive technique with high spatial resolution is the only method available that can be successfully applied, given the small amount of uranium in bone tissue. Uranium was found preferentially located in calcifying zones in exposed rats and rapidly accumulates in the endosteal and periosteal area of femoral metaphyses, in calcifying cartilage and in recently formed bone tissue along trabecular bone. Furthermore, specific localized areas with high accumulation of uranium were observed in regions identified as micro-vessels and on bone trabeculae. These observations are of high importance in the study of the accumulation of uranium in bone tissue, as the generally proposed passive chemical sorption on the surface of the inorganic part (apatite) of bone tissue cannot account for these results. Our study opens original perspectives in the field of exogenous metal bio-mineralization.

  2. Bone turnover markers during pubertal development: relationships with growth factors and adipocytokines.

    Science.gov (United States)

    Jürimäe, Jaak; Mäestu, Jarek; Jürimäe, Toivo

    2010-01-01

    The rapid increase in skeletal mass that occurs during puberty is caused by increases in longitudinal growth as well as cortical thickness. The measurement of growth changes during puberty using two-dimensional (dual-energy X-ray absorptiometry) and/or three-dimensional (computed tomography, magnetic resonance imaging) measurement devices provides only a static representation of bone tissue parameters. The measurement of bone turnover markers provides a more dynamic picture of the nature of bone tissue that can be repeated at much shorter intervals during puberty. The bone turnover markers are products of osteoblasts and osteoclasts which can be measured in urine or blood. The increase in different markers of bone turnover coincides with the pubertal growth spurt and thereafter markers decline until they converge into adult values. The initiation of puberty is accompanied by increases in androgens and estrogens. The effects of sex hormones on bone mineral accrual are mediated mainly by growth hormone and insulin-like growth factor-1, but they also exert a direct effect on bone metabolism. Important determinants of bone mineral accrual during puberty include optimal nutritional status, body composition parameters and physical activity pattern. All of these determinants are related to the state of energy balance, while peripheral indicators of energy balance, such as different growth factors and adipocytokines, may also have a positive influence of the growing skeleton. Taken together, bone mineral accrual during puberty is a complex interaction between physical activity pattern, various body composition parameters, specific growth factors and adipocytokines, and also sex hormones. Copyright © 2010 S. Karger AG, Basel.

  3. Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

    Science.gov (United States)

    Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

    2016-01-01

    Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

  4. Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jin Qi

    2017-08-01

    Full Text Available Background/Aims: Mesenchymal stem/stromal cells (MSCs are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63 and gastric cancer (SGC7901 cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

  5. Dynamic Mechanical Testing Techniques for Cortical and Cancellous Bone

    Science.gov (United States)

    Cloete, Trevor

    2017-06-01

    Bone fracture typically occurs as an impact loading event (sporting accidents, vehicle collisions), the simulation of which requires in-depth understanding of dynamic bone behavior. Bone is a natural composite material with a complex multi length-scale hierarchical microstructure. At a macroscopic level, it is classified into hard/compact cortical bone and soft/spongy cancellous (trabecular) bone, though both are low-impedance materials relative to steels. Cortical bone is predominant in long bones, while in complex bone geometries (joints, flat bones) a cancellous bone core supports a thin cortical shell. Bone has primarily been studied at quasi-static strain rates (ɛ˙ failure, with interrupted quasi-static tests revealing a strong microstructure dependence. However, bone specimens are typically destroyed during dynamic tests, leading to a lack of dynamic microstructural damage investigations. In this paper, a short overview of dynamic bone testing is presented to give context to the challenges of testing low impedance, strain-rate dependent, non-linear, visco-elastic-brittle materials. Recent state-of-the-art experimental developments in dynamic bone testing are reviewed, with emphasis on pulse shaping, momentum trapping and ISR testing. These techniques allow for dynamic bone testing at small strains and near-constant strain rates with intact specimen recovery. The results are compared to those obtained with varying strain rate tests. Interrupted dynamic test results with microstructural analysis of the recovered specimens are presented and discussed. The paper concludes with a discussion of the experimental and modeling challenges that lie ahead in the field of dynamic bone behavior. The financial assistance of the National Research Foundation and the University of Cape Town towards this research is hereby acknowledged. Opinions expressed and conclusions arrived at are those of the author alone.

  6. Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice

    OpenAIRE

    Anderson, Matthew J.; Diko, Sindi; Baehr, Leslie M.; Baar, Keith; Bodine, Sue C.; Christiansen, Blaine A.

    2016-01-01

    Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30–44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within one week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss, however it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study,...

  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 anabolic actions of GH.

  8. Effect of sex hormones on bone density during growth

    International Nuclear Information System (INIS)

    Gilsanz, V.; Roe, T.F.; Wells, T.R.; Senac, M.O. Jr.; Landing, B.; Libaneti, C.; Cann, C.E.; Schulz, E.

    1986-01-01

    The development of special phantoms permitted precise measurement of vertebral mineral content by CT in the very young. The normal standards for spinal trabecular bone of children aged 0-18 years are presented. Although there is no age-related difference in bone density before puberty, there is a significant increase in bone mineral content after puberty. The increase in sex hormones during puberty accounts for the increased density. Longitudinal studies analyzing vertebral density changes in castrated rabbits after testosterone and estradiol administration are discussed

  9. Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus).

    Science.gov (United States)

    de Margerie, E; Robin, J-P; Verrier, D; Cubo, J; Groscolas, R; Castanet, J

    2004-02-01

    Microstructure-function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones (humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3-5 weeks after hatching) and identified the associated bone tissue types ('laminar', 'longitudinal', 'reticular' or 'radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 microm day(-1) (mean 55 microm day(-1)). There was a highly significant relationship between bone tissue type and growth rate (P<10(-6)). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered (P<10(-5)) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.

  10. Mechanical Characterization of Bone: State of the Art in Experimental Approaches-What Types of Experiments Do People Do and How Does One Interpret the Results?

    Science.gov (United States)

    Bailey, Stacyann; Vashishth, Deepak

    2018-06-18

    The mechanical integrity of bone is determined by the direct measurement of bone mechanical properties. This article presents an overview of the current, most common, and new and upcoming experimental approaches for the mechanical characterization of bone. The key outcome variables of mechanical testing, as well as interpretations of the results in the context of bone structure and biology are also discussed. Quasi-static tests are the most commonly used for determining the resistance to structural failure by a single load at the organ (whole bone) level. The resistance to crack initiation or growth by fracture toughness testing and fatigue loading offers additional and more direct characterization of tissue material properties. Non-traditional indentation techniques and in situ testing are being increasingly used to probe the material properties of bone ultrastructure. Destructive ex vivo testing or clinical surrogate measures are considered to be the gold standard for estimating fracture risk. The type of mechanical test used for a particular investigation depends on the length scale of interest, where the outcome variables are influenced by the interrelationship between bone structure and composition. Advancement in the sensitivity of mechanical characterization techniques to detect changes in bone at the levels subjected to modifications by aging, disease, and/or pharmaceutical treatment is required. As such, a number of techniques are now available to aid our understanding of the factors that contribute to fracture risk.

  11. Desferrioxamine-induced long bone changes in thalassaemic patients - Radiographic features, prevalence and relations with growth

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Y.L.; Li, C.K.; Pang, L.M.; Chik, K.W

    2000-08-01

    AIM: To study the radiographic findings of desferrioxamine-induced bone dysplasia, its prevalence and relation to growth in thalassaemic patients. MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic patients on a hypertransfusion scheme and chelation therapy at a dose not exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age assessment in consecutive patients over the past 12 months were evaluated for signs of desferrioxamine-induced bone dysplasia. The findings were correlated with data on growth, chelation and body iron content. RESULTS: Twelve of 35 patients had evidence of desferrioxamine-induced long bone dysplasia. There was no significant difference in the groups with and without radiographic evidence of bone dysplasia with respect to the height percentile at time of initiation of therapy, height percentile at time of radiography, skeletal age delay, age at starting chelation, chelation dose and duration, units of blood transfused, average chelation dose, and serum ferritin levels at time of radiography. Both groups showed a reduced percentile growth with a significantly greater reduction (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine-induced bone dysplasia is associated with height reduction and can be seen in patients receiving desferrioxamine chelation therapy at doses of less than 50 mg/kg/day. Awareness of the diagnosis is of importance as reduction of the desferrioxamine dose may improve bone growth. Chan, Y. L. (2000)

  12. Bone Mineral Density in Patients with Growth Hormone Deficiency - Does a Gender Difference Exist?

    DEFF Research Database (Denmark)

    Hitz, Mette; Jensen, Jens-Erik Beck; Eskildsen, PC

    2006-01-01

    OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...

  13. Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

    DEFF Research Database (Denmark)

    Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

    2006-01-01

    OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...

  14. Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

    Science.gov (United States)

    Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

    2015-01-01

    The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may

  15. Bone density does not reflect mechanical properties in early-stage arthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, CC; Hvid, I

    2001-01-01

    : medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure...... cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests...

  16. Artificial Bone and Teeth through Controlled Ice Growth in Colloidal Suspensions

    International Nuclear Information System (INIS)

    Tomsia, Antoni P.; Saiz, Eduardo; Deville, Sylvain

    2007-01-01

    The formation of regular patterns is a common feature of many solidification processes involving cast materials. We describe here how regular patterns can be obtained in porous alumina and hydroxyapatite (HAP) by controlling the freezing of ceramic slurries followed by subsequent ice sublimation and sintering, leading to multilayered porous ceramic structures with homogeneous and well-defined architecture. These porous materials can be infiltrated with a second phase of choice to yield biomimetic nacre-like composites with improved mechanical properties, which could be used for artificial bone and teeth applications. Proper control of the solidification patterns provides powerful means of control over the final functional properties. We discuss the relationships between the experimental results, ice growth fundamentals, the physics of ice and the interaction between inert particles and the solidification front during directional freezing

  17. Incorporation of multiwalled carbon nanotubes to acrylic based bone cements: effects on mechanical and thermal properties.

    Science.gov (United States)

    Ormsby, Ross; McNally, Tony; Mitchell, Christina; Dunne, Nicholas

    2010-02-01

    Polymethyl methacrylate (PMMA) bone cement-multiwalled carbon nanotube (MWCNT) nanocomposites with a weight loading of 0.1% were prepared using 3 different methods of MWCNT incorporation. The mechanical and thermal properties of the resultant nanocomposite cements were characterised in accordance with the international standard for acrylic resin cements. The mechanical properties of the resultant nanocomposite cements were influenced by the type of MWCNT and method of incorporation used. The exothermic polymerisation reaction for the PMMA bone cement was significantly reduced when thermally conductive functionalised MWCNTs were added. This reduction in exotherm translated in a decrease in thermal necrosis index value of the respective nanocomposite cements, which potentially could reduce the hyperthermia experienced in vivo. The morphology and degree of dispersion of the MWCNTs in the PMMA matrix at different scales were analysed using scanning electron microscopy. Improvements in mechanical properties were attributed to the MWCNTs arresting/retarding crack propagation through the cement by providing a bridging effect into the wake of the crack, normal to the direction of crack growth. MWCNT agglomerations were evident within the cement microstructure, the degree of these agglomerations was dependent on the method used to incorporate the MWCNTs into the cement. Copyright 2009. Published by Elsevier Ltd.

  18. Transcriptome Profile Analysis of Mechanisms of Black and White Plumage Determination in Black-Bone Chicken

    Directory of Open Access Journals (Sweden)

    Shigang Yu

    2018-05-01

    Full Text Available Background/Aims: Melanin is a major and ubiquitous component of plumage colouration, and patterns of melanin pigmentation in birds are extremely varied. However, the molecular mechanism of pigmentation in avian plumage is still largely unknown. Methods: To elucidate the molecular mechanisms involved in the formation of black and white plumage, this study takes advantage of high-throughput sequencing technology to compare differences in the transcriptome between black and white chicken feather bulbs. In total, we constructed six cDNA libraries from black (Group B and white (Group W feather bulbs in the dorsal plumage of Muchuan black-boned chickens. Results: A comparison between Groups B and W revealed 61 differentially expressed genes, with 47 displaying higher, and 14 displaying lower, levels of expression in white feather bulbs. Our results revealed a set of candidate genes and two potential metabolic pathways involved in black-bone chicken plumage melanogenesis. These include four homeobox genes (HOXB9, HOXC8, HOXA9, and HOXC 9, two glutathione (GSH metabolism-related genes (CHAC1 and GPX3, and the transforming growth factor beta (TGF-β signalling pathway. Two known genes, TYR and MITF, were also shown to play a role in melanin formation. Conclusion: our data provide a valuable resource for discovering genes important in plumage melanin formation and will help further elucidate the molecular mechanisms for black and white plumage.

  19. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

  20. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    Science.gov (United States)

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  1. Mechanical evaluation of bone gap filled with rigid formulations castor oil polyurethane and chitosan in horses

    Directory of Open Access Journals (Sweden)

    Rodrigo Crispim Moreira

    Full Text Available ABSTRACT: Often fractures of long bones in horses are comminuted and form bone gaps, which represent a major challenge for the fixation of these fractures by loss of contact between the fragments. Bone grafts help in treating this kind of fracture and synthetic materials have been gaining ground because of the limitations of autologous and heterologous grafts. In this study were performed compressive non destructive test in 10 bones with complete cross-bone gap in mid-diaphyseal of the third metacarpal bone of horses. Using a mechanism of "crossing" the 10 bones were used in the three groups (control, castor oil poliuretane and chitosan according to the filling material. After the test with maximum load of 1000N bone had a gap filled by another material and the test was repeated. Deformations caused on the whole bone, plate and bone tissue near and distant of gap were evaluated, using strain gauges adhered to the surface at these locations. There was a reduction in bone deformation from 14% (control to 3,5% and 4,8% by filling the gap with Chitosan and castor oil respectively, and a reduction of strain on the plate of 96% and 85% by filling gap with chitosan and castor respectively. An increase in intensity and direction of deformations occurred in bone near to gap after its filling; however, there was no difference in bone deformations occurring far the gap.

  2. Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

    Science.gov (United States)

    Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

    2017-06-01

    Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Computational modeling of the mechanical modulation of the growth plate by sustained loading

    Directory of Open Access Journals (Sweden)

    Narváez-Tovar Carlos A

    2012-09-01

    Full Text Available Abstract This paper presents a computational model that describes the growth of the bone as a function of the proliferation and hypertrophy of chondrocytes in the growth plate. We have included the effects of the mechanical loads on the sizes of the proliferative and hypertrophic areas, the number of proliferative chondrocytes and the final size of the hypertrophic chondrocytes. The validation of the model was performed with experimental data published on other investigations about proximal tibia of rats, subjected to sustained axial stresses of 0.1 MPa, 0.0 MPa, -0.1 MPa and −0.2 MPa. Growth was simulated during 23 days, obtaining numerical errors between 2.77% and 3.73% with respect to experimental growth rates. The results obtained show that the model adequately simulates the behavior of the growth plate and the effect of mechanical loads over its cellular activity.

  4. The mechanism of uptake of bone-seeking isotopes by skeletal metastases

    International Nuclear Information System (INIS)

    Galasko, C.S.B.

    1977-01-01

    Although skeletal scintigraphy has become accepted as an extremely useful method of examining the skeleton, particularly for the early detection of skeletal metastases and the assessment of their response to therapy, the underlying pathological changes which allow this use of isotopes are not well understood. This study was undertaken in man and in the experimental animal in an attempt to explain the underlying mechanism for skeletal scintigraphy. Autopsy specimens indicated that tumour invasion of bone, with the possible exception of lymphomata, is associated with a significant increase in new bone production, shown by an increase in the amount of osteoid tissue and particularly immature woven bone. The animal experiments indicated that there are two mechanisms for this new bone formation. These different mechanisms may explain the different radiographic appearances. Irrespective of the mechanism of production, this new bone had a markedly increased avidity for bone-seeking isotopes. When the tumour was successfully irradiated the bone lost its osteoblastic reaction, and the production of immature new bone ceased as did the increased uptake of bone-seeking isotopes. Investigation of the vascularity of the lesion showed that there was an increase in small vessels in the neighbourhood of the tumour. The results of the study suggest that the uptake of isotope occurs in two phases. During the first phase, which occurs very rapidly, large amounts of isotope accumulate in the extracellular fluid following the increased vascularity. In the second slower phase, the isotope is gradually concentrated by the reactive immature new woven bone. (author)

  5. Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

    Directory of Open Access Journals (Sweden)

    Alison B. Shupp

    2018-06-01

    Full Text Available The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

  6. HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia.

    Science.gov (United States)

    Ota, Sara; Zhou, Zi-Qiang; Romero, Megan P; Yang, Guang; Hurlin, Peter J

    2016-10-01

    Mutations that cause increased and/or inappropriate activation of FGFR3 are responsible for a collection of short-limbed chondrodysplasias. These mutations can alter receptor trafficking and enhance receptor stability, leading to increased receptor accumulation and activity. Here, we show that wildtype and mutant activated forms of FGFR3 increase expression of the cytoplasmic deacetylase HDAC6 (Histone Deacetylase 6) and that FGFR3 accumulation is compromised in cells lacking HDAC6 or following treatment of fibroblasts or chondrocytes with small molecule inhibitors of HDAC6. The reduced accumulation of FGFR3 was linked to increased FGFR3 degradation that occurred through a lysosome-dependent mechanism. Using a mouse model of Thanatophoric Dysplasia Type II (TDII) we show that both HDAC6 deletion and treatment with the small molecule HDAC6 inhibitor tubacin reduced FGFR3 accumulation in the growth plate and improved endochondral bone growth. Defective endochondral growth in TDII is associated with reduced proliferation and poor hypertrophic differentiation and the improved bone growth was associated with increased chondrocyte proliferation and expansion of the differentiation compartment within the growth plate. These findings further define the mechanisms that control FGFR3 accumulation and contribute to skeletal pathology caused by mutations in FGFR3. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Effects of cyclic compression on the mechanical properties and calcification process of immature chick bone tissue in culture.

    Science.gov (United States)

    Maeda, Eijiro; Nakagaki, Masashi; Ichikawa, Katsuhisa; Nagayama, Kazuaki; Matsumoto, Takeo

    2017-06-01

    Contribution of mechanical loading to tissue growth during both the development and post-natal maturation is of a particular interest, as its understanding would be important to strategies in bone tissue engineering and regenerative medicine. The present study has been performed to investigate how immature bone responds to mechanical loading using an ex vivo culture system. A slice of the tibia, with the thickness of 3 mm, was obtained from 0-day-old chick. For the ex vivo culture experiment in conjunction with cyclic compressive loading, we developed a custom-made, bioreactor system where both the load and the deformation applied to the specimen was recorded. Cyclic compression, with an amplitude of 0.3 N corresponding to 1 to 2% compressive strain, was applied to immature bone specimen during a 3-day culture period at an overall loading rate 3-4 cycles/min, in the presence of β-glycerol phosphate and dexamethasone in culture medium. The stress-strain relationship was obtained at the beginning and the end of the culture experiment. In addition, analyses for alkaline phosphate release, cell viability and tissue calcification were also performed. It was exhibited that elastic moduli of bone slices were significantly elevated at the end of the 3-day culture in the presence of cyclic compression, which was a similar phenomenon to significant elevation of the elastic moduli of bone tissue by the maturation from 0-day old to 3-day old. By contrast, no significant changes in the moduli were observed in the absence of cyclic compression or in deactivated, cell-free samples. The increases in the moduli were coincided with the increase in calcified area in the bone samples. It was confirmed that immature bone can respond to compressive loading in vitro and demonstrate the growth of bone matrix, similar to natural, in vivo maturation. The elevation of the elastic moduli was attributable to the increased calcified area and the realignment of collagen fibers parallel to

  8. Effects of cyclic compression on the mechanical properties and calcification process of immature chick bone tissue in culture

    Directory of Open Access Journals (Sweden)

    Eijiro Maeda

    2017-06-01

    Full Text Available Contribution of mechanical loading to tissue growth during both the development and post-natal maturation is of a particular interest, as its understanding would be important to strategies in bone tissue engineering and regenerative medicine. The present study has been performed to investigate how immature bone responds to mechanical loading using an ex vivo culture system. A slice of the tibia, with the thickness of 3 mm, was obtained from 0-day-old chick. For the ex vivo culture experiment in conjunction with cyclic compressive loading, we developed a custom-made, bioreactor system where both the load and the deformation applied to the specimen was recorded. Cyclic compression, with an amplitude of 0.3 N corresponding to 1 to 2% compressive strain, was applied to immature bone specimen during a 3-day culture period at an overall loading rate 3–4 cycles/min, in the presence of β-glycerol phosphate and dexamethasone in culture medium. The stress-strain relationship was obtained at the beginning and the end of the culture experiment. In addition, analyses for alkaline phosphate release, cell viability and tissue calcification were also performed. It was exhibited that elastic moduli of bone slices were significantly elevated at the end of the 3-day culture in the presence of cyclic compression, which was a similar phenomenon to significant elevation of the elastic moduli of bone tissue by the maturation from 0-day old to 3-day old. By contrast, no significant changes in the moduli were observed in the absence of cyclic compression or in deactivated, cell-free samples. The increases in the moduli were coincided with the increase in calcified area in the bone samples. It was confirmed that immature bone can respond to compressive loading in vitro and demonstrate the growth of bone matrix, similar to natural, in vivo maturation. The elevation of the elastic moduli was attributable to the increased calcified area and the realignment of collagen

  9. Validation of a physical activity questionnaire to measure the effect of mechanical strain on bone mass.

    Science.gov (United States)

    Kemper, Han C G; Bakker, I; Twisk, J W R; van Mechelen, W

    2002-05-01

    Most of the questionnaires available to estimate the daily physical activity levels of humans are based on measuring the intensity of these activities as multiples of resting metabolic rate (METs). Metabolic intensity of physical activities is the most important component for evaluating effects on cardiopulmonary fitness. However, animal studies have indicated that for effects on bone mass the intensity in terms of energy expenditure (metabolic component) of physical activities is less important than the intensity of mechanical strain in terms of the forces by the skeletal muscles and/or the ground reaction forces. The physical activity questionnaire (PAQ) used in the Amsterdam Growth and Health Longitudinal Study (AGAHLS) was applied to investigate the long-term effects of habitual physical activity patterns during youth on health and fitness in later adulthood. The PAQ estimates both the metabolic components of physical activities (METPA) and the mechanical components of physical activities (MECHPA). Longitudinal measurements of METPA and MECHPA were made in a young population of males and females ranging in age from 13 to 32 years. This enabled evaluation of the differential effects of physical activities during adolescence (13-16 years), young adulthood (21-28 years), and the total period of 15 years (age 13-28 years) on bone mineral density (BMD) of the lumbar spine, as measured by dual-energy X-ray absorptiometry (DXA) in males (n = 139) and females (n = 163) at a mean age of 32 years. The PAQ used in the AGAHLS during adolescence (13-16 years) and young adulthood (21-28 years) has the ability to measure the physical activity patterns of both genders, which are important for the development of bone mass at the adult age. MECHPA is more important than METPA. The highest coefficient of 0.33 (p PAQ was established by comparing PAQ scores during four annual measurements in 200 boys and girls with two other objective measures of physical activity: movement

  10. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

    Science.gov (United States)

    Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

    2012-03-01

    Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

  11. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

    International Nuclear Information System (INIS)

    Klenke, Frank Michael; Gebhard, Martha-Maria; Ewerbeck, Volker; Abdollahi, Amir; Huber, Peter E; Sckell, Axel

    2006-01-01

    The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases

  12. Bone growth into a revised porous-coated patellar implant

    DEFF Research Database (Denmark)

    Jensen, L N; Lund, B; Gotfredsen, K

    1990-01-01

    A noncemented and clinically stable porous-coated patellar component (PCA) was removed from a patient after 11 months because of infection. It was sectioned and examined histologically in undecalcified, thin-ground sections. The bone ingrowth into the porous space was measured at eight levels. Ea...

  13. Growth patterns of fossil vertebrates as deduced from bone

    Indian Academy of Sciences (India)

    2009-10-20

    Oct 20, 2009 ... The dicynodonts on the other hand, were characterized by an overall fast growth with periodic interruptions, variable growth rates dependent on ontogeny and indeterminate growth strategy. A comparative study encompassing several neotherapsid genera including the dicynodonts shows significant ...

  14. Nitric oxide signaling in mechanical adaptation of bone

    NARCIS (Netherlands)

    Klein Nulend, J.; van Oers, R.F.M.; Bakker, A.D.; Bacabac, R.G.

    2014-01-01

    One of the most serious healthcare problems in the world is bone loss and fractures due to a lack of physical activity in elderly people as well as in bedridden patients or otherwise inactive youth. Crucial here are the osteocytes. Buried within our bones, these cells are believed to be the

  15. In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors

    Science.gov (United States)

    Gothard, David; Smith, Emma L.; Kanczler, Janos M.; Black, Cameron R.; Wells, Julia A.; Roberts, Carol A.; White, Lisa J.; Qutachi, Omar; Peto, Heather; Rashidi, Hassan; Rojo, Luis; Stevens, Molly M.; El Haj, Alicia J.; Rose, Felicity R. A. J.; Shakesheff, Kevin M.; Oreffo, Richard O. C.

    2015-01-01

    The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors. PMID:26675008

  16. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  17. The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models.

    Science.gov (United States)

    Cho, Sung-Min; Lee, Sun Haeng; Lee, Donghun; Lee, Ji Hong; Chang, Gyu Tae; Kim, Hocheol; Lee, Jin Yong

    2017-05-02

    Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 - 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P growth plate in the 300 mg/kg YJT and rhGH groups. YJT increased the longitudinal bone growth rate by stimulating chondrocyte proliferation with increasing increments of local IGF-1 and BMP-2 expression. Based on these findings, YJT may be a therapeutic candidate for the treatment of growth retardation during adolescence.

  18. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India); Mukherjee, Jayanta [Institute of Animal Health and Veterinary Biologicals, Kolkata (India); Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

    2015-04-01

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations.

  19. Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

    International Nuclear Information System (INIS)

    Nandi, Samit K.; Kundu, Biswanath; Mukherjee, Jayanta; Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna

    2015-01-01

    Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations

  20. Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries.

    Science.gov (United States)

    Baumgarten, Keith M; Oliver, Harvey A; Foley, Jack; Chen, Ding-Geng; Autenried, Peter; Duan, Shanzhong; Heiser, Patrick

    2013-05-01

    There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair. Seventy-two rats underwent repair of acute rotator cuff injuries and were randomized into the following postoperative dosing regimens: placebo, and human growth hormone at 0.1, 1, 2, 5, and 10 mg/kg/day, administered subcutaneously once per day for fourteen days (Protocol 1). An additional twenty-four rats were randomized to receive either (1) placebo or (2) human growth hormone at 5 mg/kg, administered subcutaneously twice per day for seven days preoperatively and twenty-eight days postoperatively (Protocol 2). All rats were killed twenty-eight days postoperatively. Mechanical testing was performed. Ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension were determined. For Protocol 1, analysis of variance testing showed no significant difference between the groups with regard to ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension. In Protocol 2, ultimate force to failure was significantly worse in the human growth hormone group compared with the placebo group (21.1 ± 5.85 versus 26.3 ± 5.47 N; p = 0.035). Failure was more likely to occur through the bone than the tendon-bone interface in the human growth hormone group compared with the placebo group (p = 0.001). No significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between the groups in Protocol 2. In this rat model of acute tendon-bone injury repair, daily subcutaneous postoperative human growth hormone treatment for fourteen days failed to demonstrate a significant difference in any biomechanical parameter compared with placebo. Furthermore, subcutaneous

  1. Vitamin B12–dependent taurine synthesis regulates growth and bone mass

    Science.gov (United States)

    Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

    2014-01-01

    Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

  2. Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

    Science.gov (United States)

    Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

    2012-01-01

    The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

  3. Structural characterization and mechanical performance of calcium phosphate scaffolds and natural bones: a comparative study.

    Science.gov (United States)

    Fuentes, Elena; Sáenz de Viteri, Virginia; Igartua, Amaya; Martinetti, Roberta; Dolcini, Laura; Barandika, Gotzone

    2010-01-01

    The knowledge of the mechanical response of bones and their substitutes is pertinent to numerous medical problems. Understanding the effects of mechanical influence on the body is the first step toward developing innovative treatment and rehabilitation concepts for orthopedic disorders. This was a comparative study of 5 synthetic scaffolds based on porous calcium phosphates and natural bones, with regard to their microstructural, chemical, and mechanical characterizations. The structural and chemical characterizations of the scaffolds were examined by means of X-ray diffraction, scanning electron microscopy, and X-ray spectroscopy analysis. The mechanical characterization of bones and bone graft biomaterials was carried out through compression tests using samples with noncomplex geometry. Analysis of the chemical composition, surface features, porosity, and compressive strength indicates that hydroxyapatite-based materials and trabecular bone have similar properties.

  4. [Mechanical behavior of the subchondral bone in the experimentally induced osteoarthritis].

    Science.gov (United States)

    Miyanaga, Y

    1979-06-01

    In order to evaluate the role of the subchondral bone (cancellous bone) in the development and progression of the joint degeneration, osteoarthritis of the knee joint was produced experimentally in the rabbits and viscoelasticity and strength of the subchondral bone from the femoral medial condyle have been investigated along with the pathological, histological study of the joint. The viscoelastic spectrometer and the Instron type testing machine were used. As the first change after operation, osteophyte formation around the joint margin has been observed before the initiation of the degeneration of articular cartilage and there is a possibility that mechanical properties of subchondral bone such as high deformability and low elasticity to the mechanism of osteophyte formation. Subchondral bone softening with marked increase of ultimate strain and phase lag, marked decrease of compressive elastic modulus and ultimate stress precedes or occurs concurrently with the degeneration of the articular cartilage. These facts indicate the relationship between the mechanical properties of the subchondral bone and joint degeneration. Once the joint degeneration starts, degeneration continues progressively while the subchondral bone tends to become brittle. These changes may be considered as a kind of functional adaptation to the damage or denudation of articular cartilage. It is postulated that some architectural changes of the subchondral bone may provide alterations of the mechanical properties. Biomechanical roles of the subchondral bone is suggested as one of the factors in the joint degeneration.

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

    Science.gov (United States)

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

    2015-03-01

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

  6. Chronic psychosocial stress disturbs long-bone growth in adolescent mice

    Directory of Open Access Journals (Sweden)

    Sandra Foertsch

    2017-12-01

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

  7. Age determination in manatees using growth-layer-group counts in bone

    Science.gov (United States)

    Marmontel, M.; O'Shea, T.J.; Kochman, H.I.; Humphrey, S.R.

    1996-01-01

    Growth layers were observed in histological preparations of bones of known-age, known minimum-age, and tetracycline-marked free-ranging and captive Florida manatees (Trichechus manatus latirostris), substantiating earlier preliminary findings of other studies. Detailed analysis of 17 new case histories showed that growth-layer group (GLG) counts in the periotic bone were consistent with known age, or time since tetracycline administration, but were less reliable in other bones. GLG counts were also made in periotic bones of 1,196 Florida manatees of unknown age found dead from 1974 through 1991. These counts were conducted in order to assess variability and to determine relationships among estimated age, size, sex, and degree of bone resorption. Resorption can interfere with accuracy of GLG counts. This effect does not occur until ages greater than about 15 yr and body lengths greater than 300 cm are attained. GLGs were also observed in periotic bones of Antillean manatees (Trichechus manatus manatus) but were not validated against known-age specimens. Use of GLG counts in the periotic bone is suitable for application to studies of population dynamics and other age-related aspects of manatee biology.

  8. Acceleration of bone union after structural bone grafts with a collagen-binding basic fibroblast growth factor anchored-collagen sheet for critical-size bone defects

    International Nuclear Information System (INIS)

    Ueno, Masaki; Uchida, Kentaro; Saito, Wataru; Inoue, Gen; Takahira, Naonobu; Takaso, Masashi; Matsushita, Osamu; Yogoro, Mizuki; Nishi, Nozomu; Ogura, Takayuki; Hattori, Shunji; Tanaka, Keisuke

    2014-01-01

    Bone allografts are commonly used for the repair of critical-size bone defects. However, the loss of cellular activity in processed grafts markedly reduces their healing potential compared with autografts. To overcome this obstacle, we developed a healing system for critical-size bone defects that consists of overlaying an implanted bone graft with a collagen sheet (CS) loaded with basic fibroblast growth factor (bFGF) fused to the collagen-binding domain derived from a Clostridium histolyticum collagenase (CB-bFGF). In a murine femoral defect model, defect sites treated with CS/CB-bFGF had a significantly larger callus volume than those treated with CS/native bFGF. In addition, treatment with CS/CB-bFGF resulted in the rapid formation of a hard callus bridge and a larger total callus volume at the host–graft junction than treatment with CS/bFGF. Our results suggest that the combined use of CS and CB-bFGF helps accelerate the union of allogenic bone grafts. (paper)

  9. Effects of Resveratrol Supplementation on Bone Growth in Young Rats and Microarchitecture and Remodeling in Ageing Rats

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-12-01

    Full Text Available Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day or vehicle for 3 months. Treatment effects in the tibia were examined by μ-computer tomography (μ-CT analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03. Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1 were significantly elevated in the resveratrol supplementation group (p = 0.02 with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP. These results in rat models suggest that resveratrol supplementation does not significantly affect bone

  10. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    Science.gov (United States)

    Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

    2016-08-12

    Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine's principles.

  11. Clinical study evaluating bone mineral mass in the radius during skeletal growth. Single photon absorptiometry

    Energy Technology Data Exchange (ETDEWEB)

    Hagino, Hiroshi

    1989-01-01

    Using 125-I single photon absorptiometry, bone mineral measurements were performed on 206 healthy Japanese children (2 to 19 years of age). Bone mineral content (BMC), bone width (BW) and BMC/BW values were determined for the radius at distal 1/6 site (metaphysis) and distal 1/3 site (diaphysis). BMC/BW values at both sites correlated well with body height and weight. Bone mass in the diaphysis (distal 1/3 site) increased linearly during the 2-19 years of skeletal growth, but bone mass in the metaphysis (1/6 site) increased steeply during the pubertal period. In children receiving glucocorticoid therapy, bone mass was reduced in proportion to the duration of drug administration. In children under anticonvulsant therapy, the yearly increse in bone mass was significantly low especially in those patients with poor physical activity levels. Bone mineral decrease in the radius occurred in the children with hypopituitalism, hypothyroidism (cretinism), hyperthyroidism and Turner's syndrome.

  12. 4D Shape-Preserving Modelling of Bone Growth

    DEFF Research Database (Denmark)

    Andresen, Per Rønsholt; Nielsen, Mads; Kreiborg, Sven

    1998-01-01

    From a set of temporally separated scannings of the same anatomical structure we wish to identify and analyze the growth in terms of a metamorphosis. That is, we study the tempral change of shape which may prowide an understanding of the biological processes which govern the growth process. We...

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

    Science.gov (United States)

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

    2013-04-01

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

  14. Characterisation of debris from laser and mechanical cutting of bone.

    Science.gov (United States)

    Rachmanis, Nikolaos; McGuinness, Garrett B; McGeough, Joseph A

    2014-07-01

    Laser cutting of bones has been proposed as a technology in orthopaedic surgery. In this short study, the laser-bone interaction was examined using a pulsed erbium-doped yttrium aluminium garnet laser and compared to a conventional cutting technique. Microscopic analysis revealed the nature of waste debris and showed higher proportions of finer particles for conventional sagittal sawing compared to laser cutting. © IMechE 2014.

  15. Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

    Science.gov (United States)

    Nevins, Marc L; Said, Sherif

    2017-12-28

    Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

  16. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...

  17. Effects of ultrasound on Transforming Growth Factor-beta genes in bone cells

    Directory of Open Access Journals (Sweden)

    J Harle

    2005-12-01

    Full Text Available Therapeutic ultrasound (US is a widely used form of biophysical stimulation that is increasingly applied to promote fracture healing. Transforming growth factor-beta (TGF-beta, which is encoded by three related but different genes, is known to play a major part in bone growth and repair. However, the effects of US on the expression of the TGF-beta genes and the physical acoustic mechanisms involved in initiating changes in gene expression in vitro, are not yet known. The present study demonstrates that US had a differential effect on these TGF-beta isoforms in a human osteoblast cell line, with the highest dose eliciting the most pronounced up-regulation of both TGF-beta1 and TGF-beta3 at 1 hour after treatment and thereafter declining. In contrast, US had no effect on TGF-beta2 expression. Fluid streaming rather than thermal effects or cavitation was found to be the most likely explanation for the gene responses observed in vitro.

  18. Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone.

    Science.gov (United States)

    Emilov-Velev, K; Clemente-de-Arriba, C; Alobera-García, M Á; Moreno-Sansalvador, E M; Campo-Loarte, J

    2015-01-01

    Many substances (growth factors and hormones) have osteoinduction properties and when added to some osteoconduction biomaterial they accelerate bone neoformation properties. The materials included 15 New Zealand rabbits, calcium phosphate cement (Calcibon(®)), human growth hormone (GH), and plasma rich in platelets (PRP). Each animal was operated on in both proximal tibias and a critical size bone defect of 6mm of diameter was made. The animals were separated into the following study groups: Control (regeneration only by Calcibon®), PRP (regeneration by Calcibon® and PRP), GH (regeneration by Calcibon® and GH). All the animals were sacrificed at 28 days. An evaluation was made of the appearance of the proximal extreme of rabbit tibiae in all the animals, and to check the filling of the critical size defect. A histological assessment was made of the tissue response, the presence of new bone formation, and the appearance of the biomaterial. Morphometry was performed using the MIP 45 image analyser. ANOVA statistical analysis was performed using the Statgraphics software application. The macroscopic appearance of the critical defect was better in the PRP and the GH group than in the control group. Histologically greater new bone formation was found in the PRP and GH groups. No statistically significant differences were detected in the morphometric study between bone formation observed in the PRP group and the control group. Significant differences in increased bone formation were found in the GH group (p=0.03) compared to the other two groups. GH facilitates bone regeneration in critical defects filled with calcium phosphate cement in the time period studied in New Zealand rabbits. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  19. Mutual associations among microstructural, physical and mechanical properties of human cancellous bone

    DEFF Research Database (Denmark)

    Ding, Ming; Odgaard, A; Danielsen, CC

    2002-01-01

    structure and mechanical properties. In this study, 160 cancellous bone specimens were produced from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The specimens underwent micro-CT and the microstructural properties were calculated using unbiased three-dimensional methods. The specimens...... were tested to determine the mechanical properties and the physical/compositional properties were evaluated. The type of structure together with anisotropy correlated well with Young's modulus of human tibial cancellous bone. The plate-like structure reflected high mechanical stress and the rod......-like structure low mechanical stress. There was a strong correlation between the type of trabecular structure and the bone-volume fraction. The most effective microstructural properties for predicting the mechanical properties of cancellous bone seem to differ with age....

  20. Load-adaptive bone remodeling simulations reveal osteoporotic microstructural and mechanical changes in whole human vertebrae.

    Science.gov (United States)

    Badilatti, Sandro D; Christen, Patrik; Parkinson, Ian; Müller, Ralph

    2016-12-08

    Osteoporosis is a major medical burden and its impact is expected to increase in our aging society. It is associated with low bone density and microstructural deterioration. Treatments are available, but the critical factor is to define individuals at risk from osteoporotic fractures. Computational simulations investigating not only changes in net bone tissue volume, but also changes in its microstructure where osteoporotic deterioration occur might help to better predict the risk of fractures. In this study, bone remodeling simulations with a mechanical feedback loop were used to predict microstructural changes due to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of a group of seven, mixed sex whole vertebrae, five mechanostat models mimicking different biological alterations associated with osteoporosis were developed, leading to imbalanced bone formation and resorption with a total net loss of bone tissue. A model with reduced bone formation rate and cell sensitivity led to the best match of morphometric indices compared to literature data and was chosen to predict postmenopausal osteoporotic bone loss in the whole group. Thirty years of osteoporotic bone loss were predicted with changes in morphometric indices in agreement with experimental measurements, and only showing major deviations in trabecular number and trabecular separation. In particular, although being optimized to match to the morphometric indices alone, the predicted bone loss revealed realistic changes on the organ level and on biomechanical competence. While the osteoporotic bone was able to maintain the mechanical stability to a great extent, higher fragility towards error loads was found for the osteoporotic bones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Changed morphology and mechanical properties of cancellous bone in the mandibular condyles of edentate people

    DEFF Research Database (Denmark)

    Ding, Ming

    2004-01-01

    Since edentate subjects have a reduced masticatory function, it can be expected that the morphology of the cancellous bone of their mandibular condyles has changed according to the altered mechanical environment. In the present study, the morphology of cylindrical cancellous bone specimens...

  2. Analysis of bone architecture sensitivity for changes in mechanical loading, cellular activity, mechanotransduction, and tissue properties

    NARCIS (Netherlands)

    Cox, L.G.E.; Rietbergen, van B.; Donkelaar, van C.C.; Ito, K.

    2011-01-01

    Bone has an architecture which is optimized for its mechanical environment. In various conditions, this architecture is altered, and the underlying cause for this change is not always known. In the present paper, we investigated the sensitivity of the bone microarchitecture for four factors: changes

  3. Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

    Science.gov (United States)

    Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

    2018-05-01

    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. GaN growth via HVPE on SiC/Si substrates: growth mechanisms

    Science.gov (United States)

    Sharofidinov, Sh Sh; Redkov, A. V.; Osipov, A. V.; Kukushkin, S. A.

    2017-11-01

    The article focuses on the study of GaN thin film growth via chloride epitaxy on SiC/Si hybrid substrate. SiC buffer layer was grown by a method of substitution of atoms, which allows one to reduce impact of mechanical stress therein on subsequent growth of III-nitride films. It is shown, that change in GaN growth conditions leads to change in its growth mechanism. Three mechanisms: epitaxial, spiral and stepwise growth are considered and mechanical stresses are estimated via Raman spectroscopy.

  5. Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic

    DEFF Research Database (Denmark)

    Giesen, EB; Ding, Ming; Dalstra, M

    2001-01-01

    The objective of the present study was (1) to test the hypothesis that the elastic and failure properties of the cancellous bone of the mandibular condyle depend on the loading direction, and (2) to relate these properties to bone density parameters. Uniaxial compression tests were performed......). Archimedes' principle was applied to determine bone density parameters. The cancellous bone was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than in transverse loading. High coefficients of correlation were found among the various mechanical properties and between them...

  6. Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms

    Directory of Open Access Journals (Sweden)

    Ravisha Wadhwa

    2017-06-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are currently the treatment of choice in depression and constitute major portion of prescription in depressive patients. The role of serotonin receptors in bone is emerging, raising certain questions regarding the effect of blockade of serotonin reuptake in the bone metabolism. Clinical studies have reported an association of SSRI antidepressants which with increase in fracture and decrease in bone mineral density. This review focus on recent evidence that evaluate the association of SSRIs with the risk of fracture and bone mineral density and also the probable mechanisms that might be involved in such effects.

  7. Mechanism for selective growth in electrical steel

    Science.gov (United States)

    Oh, Eun Jee; Heo, Nam Hoe; Kwon, Se Kyun; Koo, Yang Mo

    2018-01-01

    Through the competitive selective growth process between {100}, {110}, and {111} grains during final annealing which is governed by the primary grain size and the surface segregation concentration of sulfur, the sharp {110} annealing texture can be developed in a C-and Al-free Fe-3%Si-0.1%Mn electrical steel. Generally, the selective growth of the {110} grains occurs actively under the low surface segregation concentration of sulfur. In spite of the surface energy disadvantage, the selective growth of a {hkl} grain can however occur, if the {hkl} grain size is larger than the critical grain size linearly proportional to the strip thickness.

  8. The consequences of chronic kidney disease on bone metabolism and growth in children.

    Science.gov (United States)

    Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B; Wesseling-Perry, Katherine

    2012-08-01

    Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD-MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD-MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management.

  9. Neurotrophin-3 Induces BMP-2 and VEGF Activities and Promotes the Bony Repair of Injured Growth Plate Cartilage and Bone in Rats.

    Science.gov (United States)

    Su, Yu-Wen; Chung, Rosa; Ruan, Chun-Sheng; Chim, Shek Man; Kuek, Vincent; Dwivedi, Prem P; Hassanshahi, Mohammadhossein; Chen, Ke-Ming; Xie, Yangli; Chen, Lin; Foster, Bruce K; Rosen, Vicki; Zhou, Xin-Fu; Xu, Jiake; Xian, Cory J

    2016-06-01

    Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increased injury site mRNA expression was observed for neurotrophins NGF, BDNF, NT-3, and NT-4 and their Trk receptors. NT-3 and its receptor TrkC showed the highest induction. NT-3 was localized to repairing cells, whereas TrkC was observed in stromal cells, osteoblasts, and blood vessel cells at the injury site. Moreover, systemic NT-3 immunoneutralization reduced bone volume at injury sites and also reduced vascularization at the injured growth plate, whereas recombinant NT-3 treatment promoted bony repair with elevated levels of mRNA for osteogenic markers and bone morphogenetic protein (BMP-2) and increased vascularization and mRNA for vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 at the injured growth plate. When examined in vitro, NT-3 promoted osteogenesis in rat bone marrow stromal cells, induced Erk1/2 and Akt phosphorylation, and enhanced expression of BMPs (particularly BMP-2) and VEGF in the mineralizing cells. It also induced CD31 and VEGF mRNA in rat primary endothelial cell culture. BMP activity appears critical for NT-3 osteogenic effect in vitro because it can be almost completely abrogated by co-addition of the BMP inhibitor noggin. Consistent with its angiogenic effect in vivo, NT-3 promoted angiogenesis in metatarsal bone explants, an effect abolished by co-treatment with anti-VEGF. This study suggests that NT-3 may be an osteogenic and angiogenic factor upstream of BMP-2 and VEGF in bony repair, and further studies are required to investigate whether NT-3 may be a potential target for preventing growth plate faulty bony repair or for promoting bone fracture healing. © 2016

  10. Immediate Placement of Dental Implants into Fresh Extraction Socket of Periapical Lesion with Bone Augmentation Using Growth Factors (PRGF) and Graft Bone (Bio-Oss)

    OpenAIRE

    Piuryk, V. P.; Kareem, Shujairi Ahmed

    2016-01-01

    Immediate implant placement and loading can be done in a compromised bone. Curettage, cleaning of the whole area up to good bone quality and primary stability are the main necessities for success. The effect of local application of scaffold-like preparation rich in growth factors (PRGF) on bone regeneration in artificial defects and the potential effect of humidifying titanium dental implants with liquid PRGF on their osseointegration were investigated. The PRGF formulations were obtained fro...

  11. The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1

    International Nuclear Information System (INIS)

    Scarantino, C.W.; Rubin, P.; Constine, L.S. III

    1984-01-01

    Bone marrow regeneration following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation to large volumes of bone marrow does not completely suppress bone marrow regeneration but results in a rapid compensatory response. Comparisons are made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow indicate significantly different response mechanisms. (Auth.)

  12. Mechanical Modelling of Cancellous Bone from their Microstructure

    Directory of Open Access Journals (Sweden)

    Ruiz–Cervantes O.

    2010-04-01

    Full Text Available In this paper is established a spongy bone bidimensional models methodology for its analysis by finite element software. The models are focused to represent the bone trabecular structure by Voronoi cells, using the coordinates of the porous center, contained within the bone structure, obtained by optical microscope images. Looking for a better geometrical similarity, it was assigned a thicker transversal area in the trabecula union zone, because has been reported that this factor gives a better approximation to experimental results. To feed the finite element models, compression test has been done to trabecular specimens, taking the maximum strain and maximum stress, to obtain the elastic modulus. By means of strained specimen images analysis, it has been established the structure collapse moment. It was when the 36% of total trabeculae failed. Finally it was obtained a tissue Young modulus of 323 [MPa] and with this value, the resistance variation in function of density and trabecular architecture.

  13. Advances in the understanding of crystal growth mechanisms

    CERN Document Server

    Nishinaga, T; Harada, J; Sasaki, A; Takei, H

    1997-01-01

    This book contains the results of a research project entitled Crystal Growth Mechanisms on an Atomic Scale, which was carried out for 3 years by some 72 reseachers. Until recently in Japan, only the technological aspects of crystal growth have been emphasized and attention was paid only to its importance in industry. However the scientific aspects also need to be considered so that the technology of crystal growth can be developed even further. This project therefore aimed at understanding crystal growth and the emphasis was on finding growth mechanisms on an atomic scale.

  14. Spatial and temporal variations of the callus mechanical properties during bone transport

    Energy Technology Data Exchange (ETDEWEB)

    Mora-Macias, J.; Reina-Romo, E.; Pajares, A.; Miranda, P.; Dominguez, J.

    2016-07-01

    Nanoindentation allows obtaining the elastic modulus and the hardness of materials point by point. This technique has been used to assess the mechanical propeties of the callus during fracture healing. However, as fas as the authors know, the evaluation of mechanical properties by this technique of the distraction and the docking-site calluses generated during bone transport have not been reported yet. Therefore, the aim of this work is using nanoindentation to assess the spatial and temporal variation of the elastic modulus of the woven bone generated during bone transport. Nanoindentation measurements were carried out using 6 samples from sheep sacrificed at different stages of the bone transport experiments. The results obtained show an important heterogeneity of the elastic modulus of the woven bone without spatial trends. In the case of temporal variation, a clear increase of the mean elastic modulus with time after surgery was observed (from 7±2GPa 35 days after surgery to 14±2GPa 525 days after surgery in the distraction callus and a similar increase in the docking site callus). Comparison with the evolution of the elastic modulus in the woven bone generated during fracture healing shows that mechanical properties increase slower in the case of the woven bone generated during bone transport. (Author)

  15. Dynamics of body composition and bone in patients with juvenile idiopathic arthritis treated with growth hormone.

    Science.gov (United States)

    Bechtold, Susanne; Ripperger, Peter; Dalla Pozza, Robert; Roth, Johannes; Häfner, Renate; Michels, Hartmut; Schwarz, Hans Peter

    2010-01-01

    GH has a positive impact on growth, bone, and muscle development. The objectives of this study were to demonstrate the effects of GH treatment on regional body composition and bone geometry at final height in patients with juvenile idiopathic arthritis (JIA). In this longitudinal study, parameters of bone mineral density and geometry as well as muscle and fat cross-sectional area (CSA) in the nondominant forearm were recorded using peripheral quantitative computed tomography at yearly intervals until final height in 12 patients (seven females) receiving GH treatment. Data at final height were compared with 13 patients (nine females) with JIA not treated with GH. Patients were treated with GH for a mean of 5.35 +/- 0.7 yr. Correcting for height, total bone CSA (+0.89 +/- 0.5 sd) and muscle CSA (+1.14 +/- 0.6 sd) increased significantly and normalized at final height. Compared with JIA patients without GH at final height, there was a significantly higher muscle CSA and a lower fat CSA in GH-treated patients. Additionally, in relation to total bone CSA, there was significantly more cortical and less marrow CSA in boys with GH treatment. During GH treatment, there was a significant increase and normalization of total bone and muscle CSA at final height. In accordance with an anabolic effect of GH, fat mass stabilized at the lower limit of healthy children. At final height, cortical and marrow CSA, relative to total bone CSA, were normalized in GH-treated patients.

  16. The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts.

    Science.gov (United States)

    Sönmez, Tolga Taha; Bayer, Andreas; Cremer, Tillman; Hock, Jennifer Vanessa Phi; Lethaus, Bernd; Kweider, Nisreen; Wruck, Christoph Jan; Drescher, Wolf; Jahr, Holger; Lippross, Sebastian; Pufe, Thomas; Tohidnezhad, Mersedeh

    2017-11-01

    Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss ® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss ® in ethanol (EtOH) treated osteoblasts. The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss ® were assessed. The application of PRGF and Bio-Oss ® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss ® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss ® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells. These results indicate that the simultaneous application of PRGF and Bio-Oss ® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1.

    Directory of Open Access Journals (Sweden)

    Karine Z Oben

    Full Text Available An understanding of how each individual 5q chromosome critical deleted region (CDR gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs. Early Growth Response 1 (EGR1 is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell quiescence as well as the master regulator of apoptosis-p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.

  18. Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

    International Nuclear Information System (INIS)

    Olsen, O E; Wader, K F; Misund, K; Våtsveen, T K; Rø, T B; Mylin, A K; Turesson, I; Størdal, B F; Moen, S H; Standal, T; Waage, A; Sundan, A; Holien, T

    2014-01-01

    Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8–809) compared with healthy controls (median 110 pg/ml, range 8–359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma

  19. Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.

    Science.gov (United States)

    Ammann, Patrick; Brennan, Tara C; Mekraldi, Samia; Aubert, Michel L; Rizzoli, René

    2010-06-01

    Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Human brain activity associated with painful mechanical stimulation to muscle and bone

    OpenAIRE

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-01-01

    Purpose The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Methods Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain ac...

  1. Concise review: Bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications.

    OpenAIRE

    Wright, KT; El Masri, W; Osman, A; Chowdhury, J; Johnson, WEB

    2011-01-01

    Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversi...

  2. Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

    Science.gov (United States)

    Orth, Lucas E; O'Mara, Keliana L

    2018-01-01

    This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

  3. [Effect of growth hormone combined with Radix Dipsaci on the body growth and the bone metabolism of hypophysectomized rats].

    Science.gov (United States)

    Liu, Ying-ke; Zhang, Zhi-xin; Zhang, Qiong

    2011-12-01

    To study the effect of growth hormone (GH) combined with Radix Dipsaci on the body growth and the bone mineral content (BMC) of hypophysectomized rats. The GH deficiency rats model was established using the hypophysectomized operation through the skull and the throat. Qualified rats were divided into the sham-operation group (n = 15), the negative control group (n = 13), the GH intervention group (n = 13), and the GH combined with Radix Dipsaci group(n = 12). GH (0.25 mg/kg) was subcutaneously injected from the cervical part in the GH intervention group and the GH combined with Radix Dipsaci group at the same time, while equal volume of normal saline was injected to the rest groups. 0.7 mL/100 kg Radix Dipsaci was given by gastrogavage to the GH combined with Radix Dipsaci group at the same time, while equal volume of normal saline was given by gastrogave to the rest groups. The body weight, the tail length, and the body length were measured during the intervention period. Blood was withdrawn after 14-day intervention. The femoral bone and the tibial bone were taken out. The levels of GH, insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), and osteocalcin (OC) were measured. The width of the tibial epiphyseal plate was measured. The bilateral femur bone mineral density (BMD) and BMC were measured using the dual energy X-ray absorptiometry. The body weight, the body length, the length of the femoral bone, the length of the tibial bone, the width of the epiphyseal plate, the levels of the GH, IGF-1, ALP, and OC increased in the GH intervention group and the GH combined with Radix Dipsaci group after 2-week intervention, showing statistical difference when compared with the model group (P 0.05). There was insignificant difference in the aforesaid indices between the two groups (P > 0.05). Compared with the model group, the BMD of the GH combined with Radix Dipsaci group increased with statistical difference (P growth. But it could elevate BMD and BMC

  4. Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice.

    Science.gov (United States)

    Anderson, Matthew J; Diko, Sindi; Baehr, Leslie M; Baar, Keith; Bodine, Sue C; Christiansen, Blaine A

    2016-10-01

    Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. The effects of oestrogens on linear bone growth

    DEFF Research Database (Denmark)

    Juul, A

    2001-01-01

    boys, and non-aromatizable androgens [oxandrolone or dihydrotestosterone (DHT)] have no effect on GH secretion. Treatment with aromatase inhibitors reduces circulating IGF-I concentrations in healthy males, and reduces growth in boys with testotoxicosis. Taken together, these findings suggest...

  6. Relationships among ultrasonic and mechanical properties of cancellous bone in human calcaneus in vitro.

    Science.gov (United States)

    Wear, Keith A; Nagaraja, Srinidhi; Dreher, Maureen L; Sadoughi, Saghi; Zhu, Shan; Keaveny, Tony M

    2017-10-01

    Clinical bone sonometers applied at the calcaneus measure broadband ultrasound attenuation and speed of sound. However, the relation of ultrasound measurements to bone strength is not well-characterized. Addressing this issue, we assessed the extent to which ultrasonic measurements convey in vitro mechanical properties in 25 human calcaneal cancellous bone specimens (approximately 2×4×2cm). Normalized broadband ultrasound attenuation, speed of sound, and broadband ultrasound backscatter were measured with 500kHz transducers. To assess mechanical properties, non-linear finite element analysis, based on micro-computed tomography images (34-micron cubic voxel), was used to estimate apparent elastic modulus, overall specimen stiffness, and apparent yield stress, with models typically having approximately 25-30 million elements. We found that ultrasound parameters were correlated with mechanical properties with R=0.70-0.82 (pmechanical properties beyond that provided by bone quantity alone (p≤0.05). Adding ultrasound variables to linear regression models based on bone quantity improved adjusted squared correlation coefficients from 0.65 to 0.77 (stiffness), 0.76 to 0.81 (apparent modulus), and 0.67 to 0.73 (yield stress). These results indicate that ultrasound can provide complementary (to bone quantity) information regarding mechanical behavior of cancellous bone. Published by Elsevier Inc.

  7. Wear and Mechanical Behaviour of Various Polymethylmethacrylate Bone Cements

    Czech Academy of Sciences Publication Activity Database

    Balko, J.; Ballóková, B.; Jakubéczyová, D.; Hvizdoš, P.; Hloch, Sergej; Kloc, J.; Monka, P.

    2013-01-01

    Roč. 13, č. 1 (2013), s. 34-43 ISSN 1335-8987 Institutional support: RVO:68145535 Keywords : bone cements * mixing * pin-on-plate * porosity * nano-hardness Subject RIV: JQ - Machines ; Tools http://www.imr.saske.sk/pmp/issue/1-2013/PMP_Vol13_No1_p_034-043.pdf

  8. Selection of phosphorus solubilizing bacteria with biocontrol potential for growth in phosphorus rich animal bone charcoal

    NARCIS (Netherlands)

    Postma, J.; Nijhuis, E.H.; Sommeus, E.

    2010-01-01

    Bacteria with the ability to solubilize phosphorus (P) and to improve plant health were selected and tested for growth and survival in P-rich animal bone charcoal (ABC). ABC is suggested to be suitable as a carrier for biocontrol agents, offering them a protected niche as well as delivering

  9. Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis

    NARCIS (Netherlands)

    van Tok, Melissa N.; Yeremenko, Nataliya G.; Teitsma, Christine A.; Kream, Barbara E.; Knaup, Véronique L.; Lories, Rik J.; Baeten, Dominique L.; van Duivenvoorde, Leonie M.

    2016-01-01

    Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could

  10. Bone mineral density and body composition in Noonan's syndrome: effects of growth hormone treatment

    NARCIS (Netherlands)

    Noordam, C.; Span, J.; van Rijn, R. R.; Gomes-Jardin, E.; van Kuijk, C.; Otten, B. J.

    2002-01-01

    We assessed bone mineral density (BMD) and body composition in children with Noonan's syndrome (NS) before and during growth hormone (GH) treatment. Sixteen children (12 boys, 4 girls) with NS aged 5.8-14.2 (mean 10.0) years were studied for 2 years. Anthropometry, BMD measurements by radiographic

  11. Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

    NARCIS (Netherlands)

    Boot, Annemieke M.; van der Sluis, Inge M.; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

    2009-01-01

    Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray

  12. The Histone Deacetylase Inhibitor, Vorinostat, Reduces Tumor Growth at the Metastatic Bone Site and Associated Osteolysis, but Promotes Normal Bone Loss

    OpenAIRE

    Pratap, Jitesh; Akech, Jacqueline; Wixted, John J.; Szabo, Gabriela; Hussain, Sadiq; McGee-Lawrence, Meghan E.; Li, Xiaodong; Bedard, Krystin; Dhillon, Robinder J.; van Wijnen, Andre J.; Stein, Janet L.; Stein, Gary S.; Westendorf, Jennifer J.; Lian, Jane B.

    2010-01-01

    Vorinostat, an oral histone deacetylase inhibitor with anti-tumor activity, is in clinical trials for hematological and solid tumors that metastasize and compromise bone structure. Consequently, there is a requirement to establish the effects of vorinostat on tumor growth within bone. Breast (MDA-231) and prostate (PC3) cancer cells were injected into tibias of SCID/NCr mice and the effects of vorinostat on tumor growth and osteolytic disease were assessed by radiography, μCT, histological an...

  13. Administration of Clinoptilolite to Broiler Chickens During Growth and Its Effect on the Growth Rate and Bone Metabolism Indicators

    Directory of Open Access Journals (Sweden)

    E. Straková

    2008-01-01

    Full Text Available The growth rate and bone metabolism indicators were monitored in broiler chickens receiving the feed supplemented with clinoptilolite. One-day-old broiler chickens ROSS 308 were divided into control (C and experimental (E groups with 100 males and 100 females per group. The chickens received the complete feed mixture BR1 from 1 to 10 days of age, followed by the feed mixture BR2 until the age of 30 days, and the feed mixture BR3 until the end of the experiment (40 days. The feed mixtures of the experimental group were supplemented with clinoptilolite (commercial additive ZeoFeed at a level of 0.5% (BR1, 1.5% (BR2 and 2.5% (BR3, replacing the corresponding portion of wheat. Feed mixtures and drinking water were provided ad libitum. The live weight of broiler chickens in both the control and experimental group increased steadily during the experiment. At the end of the experiment, live weights of experimental females (2,416 g and males (2,829 g were higher than those of control females (2,345 g and males (2,694 g by 3% and 5%, respectively. Significant differences in the live weight between groups were found from the age of 30 days (P ⪬ 0.05 and P ⪬ 0.01. At the age of 40 days, the chickens were slaughtered and the femur and tibiotarsus of the right leg were analysed for the content of dry matter, ash, calcium, phosphorus and magnesium. The ash content in dry matter ranged from 53.0 to 54.1% in group C and from 51.7 to 53.2% in group E. The Ca and P contents in dry matter in group E were lower than those in group C, except for Ca and P in the male tibiotarsus. In both groups, regardless of sex, the ash content was higher in the tibiotarsus than in the femur. Since fat levels in bones of the experimental group were increased (females by 19.5% in the femur and 21.3% in the tibiotarsus; males by 22.0% in the femur and 26.3% in the tibiotarsus, which could affect the values obtained, ash, calcium, phosphorus and magnesium were determined in the

  14. Seasonal bone growth and physiology in endotherms shed light on dinosaur physiology.

    Science.gov (United States)

    Köhler, Meike; Marín-Moratalla, Nekane; Jordana, Xavier; Aanes, Ronny

    2012-07-19

    Cyclical growth leaves marks in bone tissue that are in the forefront of discussions about physiologies of extinct vertebrates. Ectotherms show pronounced annual cycles of growth arrest that correlate with a decrease in body temperature and metabolic rate; endotherms are assumed to grow continuously until they attain maturity because of their constant high body temperature and sustained metabolic rate. This apparent dichotomy has driven the argument that zonal bone denotes ectotherm-like physiologies, thus fuelling the controversy on dinosaur thermophysiology and the evolution of endothermy in birds and mammal-like reptiles. Here we show, from a comprehensive global study of wild ruminants from tropical to polar environments, that cyclical growth is a universal trait of homoeothermic endotherms. Growth is arrested during the unfavourable season concurrently with decreases in body temperature, metabolic rate and bone-growth-mediating plasma insulin-like growth factor-1 levels, forming part of a plesiomorphic thermometabolic strategy for energy conservation. Conversely, bouts of intense tissue growth coincide with peak metabolic rates and correlated hormonal changes at the beginning of the favourable season, indicating an increased efficiency in acquiring and using seasonal resources. Our study supplies the strongest evidence so far that homeothermic endotherms arrest growth seasonally, which precludes the use of lines of arrested growth as an argument in support of ectothermy. However, high growth rates are a distinctive trait of mammals, suggesting the capacity for endogenous heat generation. The ruminant annual cycle provides an extant model on which to base inferences regarding the thermophysiology of dinosaurs and other extinct taxa.

  15. The molecular response of bone to growth hormone during skeletal unloading: regional differences

    Science.gov (United States)

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

    1995-01-01

    Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone

  16. Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Choi

    Full Text Available Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days. Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed, and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

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

    Directory of Open Access Journals (Sweden)

    DB Jones

    2003-03-01

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

  18. Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle.

    Science.gov (United States)

    Gazit, D; Ehrlich, J; Kohen, Y; Bab, I

    1987-09-01

    Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5-21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.

  19. Mechanical growth and morphogenesis of seashells

    KAUST Repository

    Moulton, D.E.; Goriely, A.; Chirat, R.

    2012-01-01

    . However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell

  20. Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

    International Nuclear Information System (INIS)

    Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J.

    2005-01-01

    The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

  1. A comparative investigation of bone surface after cutting with mechanical tools and Er:YAG laser.

    Science.gov (United States)

    Baek, Kyung-Won; Deibel, Waldemar; Marinov, Dilyan; Griessen, Mathias; Dard, Michel; Bruno, Alfredo; Zeilhofer, Hans-Florian; Cattin, Philippe; Juergens, Philipp

    2015-07-01

    Despite of the long history of medical application, laser ablation of bone tissue became successful only recently. Laser bone cutting is proven to have higher accuracy and to increase bone healing compared to conventional mechanical bone cutting. But the reason of subsequent better healing is not biologically explained yet. In this study we present our experience with an integrated miniaturized laser system mounted on a surgical lightweight robotic arm. An Erbium-doped Yttrium Aluminium Garnet (Er:YAG) laser and a piezoelectric (PZE) osteotome were used for comparison. In six grown up female Göttingen minipigs, comparative surgical interventions were done on the edentulous mandibular ridge. Our laser system was used to create different shapes of bone defects on the left side of the mandible. On the contralateral side, similar bone defects were created by PZE osteotome. Small bone samples were harvested to compare the immediate post-operative cut surface. The analysis of the cut surface of the laser osteotomy and conventional mechanical osteotomy revealed an essential difference. The scanning electron microscopy (SEM) analysis showed biologically open cut surfaces from the laser osteotomy. The samples from PZE osteotomy showed a flattened tissue structure over the cut surface, resembling the "smear layer" from tooth preparation. We concluded that our new finding with the mechanical osteotomy suggests a biological explanation to the expected difference in subsequent bone healing. Our hypothesis is that the difference of surface characteristic yields to different bleeding pattern and subsequently results in different bone healing. The analyses of bone healing will support our hypothesis. © 2015 Wiley Periodicals, Inc.

  2. [The effects of strontium in drinking water on growth and development of rat bone].

    Science.gov (United States)

    Xu, F; Zhang, X; Liu, J; Fan, M

    1997-05-01

    Effects of strontium at a high level in drinking water on growth and development of rat bone were studied. The results showed that Sr2+ concentration from 5 to 500 mg/L in drinking water could increase the contents of strontium in blood serum, urine, femur, mixilla and tooth in Wistar rats exposed to Sr2+ for 12 weeks with an obvious dose-response relationship. In addition, strontium at over 50 mg/L could decrease the contents of calcium in bone, increase the contents of calcium in tooth and bone density, and decrease the levels of calcium in blood serum except female rats at the 12th week. Effects of Sr2+ on body weight, body length, AKP activity of serum, calcium content of urine and breaking load of bended femur for rats were not found. However, there are differences in the effects of strontium on growth and development of bone between male and female rats. At the 12th week the content of calcium in blood serum decreased in male rats but increased in female rats in exposed groups. At the 4th and 8th weeks, urine Hop/Cr in male rats increased but it remained normal level in female rats. Sr2+ increased the bone density of mixilla in male rats but it did not increase that of femur in female rats. It is suggested that such changes may be a result of the differences in endocritic regulation and metabolic process between two sexes.

  3. The mechanical properties of broiler chicken bones affected by ...

    African Journals Online (AJOL)

    The first group (Zn50) was fed commercial basal diet with no Zn additives (zinc content- 50 mg/kg feed). The second group ... In group Zn100, significantly increased values of bone cross-section area (Ar) were observed on days 14 and 35 and moment of inertia (I) on days 14, 21 and 35 (P<0.05). Results suggested that the ...

  4. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice.

    Science.gov (United States)

    Garcia, Stéphanie; Dirat, Béatrice; Tognacci, Thomas; Rochet, Nathalie; Mouska, Xavier; Bonnafous, Stéphanie; Patouraux, Stéphanie; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Gennero, Isabelle; Gouze, Elvire

    2013-09-18

    Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.

  5. Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance.

    Science.gov (United States)

    Kanai, Yugo; Yasoda, Akihiro; Mori, Keita P; Watanabe-Takano, Haruko; Nagai-Okatani, Chiaki; Yamashita, Yui; Hirota, Keisho; Ueda, Yohei; Yamauchi, Ichiro; Kondo, Eri; Yamanaka, Shigeki; Sakane, Yoriko; Nakao, Kazumasa; Fujii, Toshihito; Yokoi, Hideki; Minamino, Naoto; Mukoyama, Masashi; Mochizuki, Naoki; Inagaki, Nobuya

    2017-11-01

    Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.

  6. Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India); Basu, Debabrata [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India)

    2013-04-01

    Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. - Highlights: ► Fabrication and characterization of porous chitosan with or without IGF-1 and BMP-2 ► Highly porous growth factor loaded chitosan studied in animal subjects for 3 months ► Parameters studied: histopathology, radiology and fluorochrome labeling ► IGF-1 loaded porous chitosan found to be very effective for bone defect healing.

  7. Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

    International Nuclear Information System (INIS)

    Nandi, Samit K.; Kundu, Biswanath; Basu, Debabrata

    2013-01-01

    Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. - Highlights: ► Fabrication and characterization of porous chitosan with or without IGF-1 and BMP-2 ► Highly porous growth factor loaded chitosan studied in animal subjects for 3 months ► Parameters studied: histopathology, radiology and fluorochrome labeling ► IGF-1 loaded porous chitosan found to be very effective for bone defect healing

  8. Portraying mechanics of plant growth promoting rhizobacteria (PGPR: A review

    Directory of Open Access Journals (Sweden)

    Dweipayan Goswami

    2016-12-01

    Full Text Available Population growth and increase in food requirement is the global problem. It is inevitable to introduce new practices that help to increase agricultural productivity. Use of plant growth promoting rhizobacteria (PGPR has shown potentials to be a promising technique in the practice of sustainable agriculture. A group of natural soil microbial flora acquire dwelling in the rhizosphere and on the surface of the plant roots which impose beneficial effect on the overall well-being of the plant are categorized as PGPR. Researchers are actively involved in understanding plant growth promoting mechanics employed by PGPR. Broadly, these are divided into direct and indirect mechanics. Any mechanism that directly enhances plant growth either by providing nutrients or by producing growth regulators are portrayed as direct mechanics. Whereas, any mechanisms that protects plant from acquiring infections (biotic stress or helps plant to grow healthily under environmental stresses (abiotic stress are considered indirect mechanics. This review is focused to describe cogent mechanics employed by PGPR that assists plant to sustain healthy growth. Also, we emphasized on the PGPR-based products which have been commercially developed exploiting these mechanics of PGPR.

  9. Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

    Science.gov (United States)

    Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

    2018-06-01

    Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

  10. [Bone Cell Biology Assessed by Microscopic Approach. Response to mechanical stress by osteocyte network].

    Science.gov (United States)

    Komori, Toshihisa

    2015-10-01

    Osteocytes were considered to be involved in the response to mechanical stress from their network structure. However, it was difficult to prove the function because of the lack of animal models for a long time. Recently, the function of osteocytes was clarified using various knockout and transgenic mice. Osteocyte death causes bone remodeling, which is a repair process induced by osteocyte necrosis but not by the loss of the function of live osteocytes. The osteocyte network mildly inhibits bone formation and mildly stimulates bone resorption in physiological condition. In unloaded condition, it strongly inhibits bone formation and strongly stimulates bone resorption, at least in part, through the induction of Sost in osteocytes and Rankl in osteoblasts.

  11. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind...... of periosteal BFR/BS (2-fold increase vs. BTX, Pmuscle mass (+29% vs. BTX, Pmuscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse......BMD, -13%, Pmuscle mass (-69%, Pmuscle cell cross sectional area (CSA) (-73%, P

  12. Growth mechanisms, polytypism, and real structure of kaolinite microcrystals

    International Nuclear Information System (INIS)

    Samotoin, N. D.

    2008-01-01

    The mechanisms of growth of kaolinite microcrystals (0.1-5.0 μm in size) at deposits related to the cluvial weathering crust, as well as to the low-temperature and medium-temperature hydrothermal processes of transformations of minerals in different rocks in Russia, Kazakhstan, Ukraine, Czechia, Vietnam, India, Cuba, and Madagascar, are investigated using transmission electron microscopy and vacuum decoration with gold. It is established that kaolinite microcrystals grow according to two mechanisms: the mechanism of periodic formation of two-dimensional nuclei and the mechanism of spiral growth. The spiral growth of kaolinite microcrystals is dominant and occurs on steps of screw dislocations that differ in sign and magnitude of the Burgers vector along the c axis. The layered growth of kaolinite originates from a widespread source in the form of a step between polar (+ and -) dislocations, i.e., a growth analogue of the Frank-Read dislocation source. The density of growth screw dislocations varies over a wide range and can be as high as ∼10 9 cm -2 . Layered stepped kaolinite growth pyramids for all mechanisms of growth on the (001) face of kaolinite exhibit the main features of the triclinic 1Tc and real structures of this mineral.

  13. Insulin-like growth factor I has independent effects on bone matrix formation and cell replication

    International Nuclear Information System (INIS)

    Hock, J.M.; Centrella, M.; Canalis, E.

    1988-01-01

    The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3- 3 H]proline and [methyl- 3 H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [ 3 H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [ 3 H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis

  14. Geometric and mechanical properties evaluation of scaffolds for bone tissue applications designing by a reaction-diffusion models and manufactured with a material jetting system

    Directory of Open Access Journals (Sweden)

    Marco A. Velasco

    2016-10-01

    Full Text Available Scaffolds are essential in bone tissue engineering, as they provide support to cells and growth factors necessary to regenerate tissue. In addition, they meet the mechanical function of the bone while it regenerates. Currently, the multiple methods for designing and manufacturing scaffolds are based on regular structures from a unit cell that repeats in a given domain. However, these methods do not resemble the actual structure of the trabecular bone which may work against osseous tissue regeneration. To explore the design of porous structures with similar mechanical properties to native bone, a geometric generation scheme from a reaction-diffusion model and its manufacturing via a material jetting system is proposed. This article presents the methodology used, the geometric characteristics and the modulus of elasticity of the scaffolds designed and manufactured. The method proposed shows its potential to generate structures that allow to control the basic scaffold properties for bone tissue engineering such as the width of the channels and porosity. The mechanical properties of our scaffolds are similar to trabecular tissue present in vertebrae and tibia bones. Tests on the manufactured scaffolds show that it is necessary to consider the orientation of the object relative to the printing system because the channel geometry, mechanical properties and roughness are heavily influenced by the position of the surface analyzed with respect to the printing axis. A possible line for future work may be the establishment of a set of guidelines to consider the effects of manufacturing processes in designing stages.

  15. Mechanisms of pancreatic beta-cell growth and regeneration

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1989-01-01

    Information about the mechanism of beta-cell growth and regeneration may be obtained by studies of insulinoma cells. In the present study the growth and function of the rat insulinoma cell lines RINm5F and 5AH were evaluated by addition of serum, hormones, and growth factors. It was found...... of insulin mRNA content showed that the insulinoma cells only contained about 2% of that of normal rat beta-cells. These results are discussed in relation to the role of growth factors, oncogenes, and differentiation in the growth and regeneration of beta-cells....... that transferrin is the only obligatory factor whereas growth hormone, epidermal growth factor, fibroblast growth factor, and TRH had modulating effects. A heat-labile heparin binding serum factor which stimulated thymidine incorporation but not cell proliferation was demonstrated in human serum. Measurements...

  16. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    Directory of Open Access Journals (Sweden)

    Francesca Marini

    2016-08-01

    Full Text Available Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2, the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs. Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles.

  17. Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density

    Science.gov (United States)

    2010-11-01

    induced expression of both type-I collagen and bone sialoprotein by 2-fold and down regulated MMP-9, TRAP, Sodium- potassium pump, and Cathespin K by 3-, 5...assayed with the bicinchoninic acid method. Ten g of extract protein from each extract was loaded onto 10% SDS- polyacryl - amide gels and transblotted...caused down regulation of BR genes MMP-9, TRAP and Sodium- potassium pump by 3, 5, and 2-fold respectively (pɘ.0001). In contrast, the expression of

  18. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  19. Circulating levels of IGF-1 directly regulate bone growth and density

    Science.gov (United States)

    Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek

    2002-01-01

    IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108

  20. Intraoperative mechanical measurement of bone quality with the DensiProbe.

    Science.gov (United States)

    Hoppe, Sven; Uhlmann, Michael; Schwyn, Robert; Suhm, Norbert; Benneker, Lorin M

    2015-01-01

    Reduced bone stock can result in fractures that mostly occur in the spine, distal radius, and proximal femur. In case of operative treatment, osteoporosis is associated with an increased failure rate. To estimate implant anchorage, mechanical methods seem to be promising to measure bone strength intraoperatively. It has been shown that the mechanical peak torque correlates with the local bone mineral density and screw failure load in hip, hindfoot, humerus, and spine in vitro. One device to measure mechanical peak torque is the DensiProbe (AO Research Institute, Davos, Switzerland). The device has shown its effectiveness in mechanical peak torque measurement in mechanical testing setups for the use in hip, hindfoot, and spine. In all studies, the correlation of mechanical torque measurement and local bone mineral density and screw failure load could be shown. It allows the surgeon to judge local bone strength intraoperatively directly at the region of interest and gives valuable information if additional augmentation is needed. We summarize methods of this new technique, its advantages and limitations, and give an overview of actual and possible future applications. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  1. Mechanisms Inducing Low Bone Density in Duchenne Muscular Dystrophy in Mice and Humans

    Science.gov (United States)

    Rufo, Anna; Del Fattore, Andrea; Capulli, Mattia; Carvello, Francesco; De Pasquale, Loredana; Ferrari, Serge; Pierroz, Dominique; Morandi, Lucia; De Simone, Michele; Rucci, Nadia; Bertini, Enrico; Bianchi, Maria Luisa; De Benedetti, Fabrizio; Teti, Anna

    2011-01-01

    Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro–computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. © 2011 American Society for Bone and Mineral Research PMID:21509823

  2. Simulated weightlessness and synbiotic diet effects on rat bone mechanical strength

    Science.gov (United States)

    Sarper, Hüseyin; Blanton, Cynthia; DePalma, Jude; Melnykov, Igor V.; Gabaldón, Annette M.

    2014-10-01

    This paper reports results on exposure to simulated weightlessness that leads to a rapid decrease in bone mineral density known as spaceflight osteopenia by evaluating the effectiveness of dietary supplementation with synbiotics to counteract the effects of skeletal unloading. Forty adult male rats were studied under four different conditions in a 2 × 2 factorial design with main effects of diet (synbiotic and control) and weight condition (unloaded and control). Hindlimb unloading was performed at all times for 14 days followed by 14 days of recovery (reambulation). The synbiotic diet contained probiotic strains Lactobacillus acidophilus and Lactococcus lactis lactis and prebiotic fructooligosaccharide. This paper also reports on the development of a desktop three-point bending device to measure the mechanical strength of bones from rats subjected to simulated weightlessness. The importance of quantifying bone resistance to breakage is critical when examining the effectiveness of interventions against osteopenia resulting from skeletal unloading, such as astronauts experience, disuse or disease. Mechanical strength indices provide information beyond measures of bone density and microarchitecture that enhance the overall assessment of a treatment's potency. In this study we used a newly constructed three-point bending device to measure the mechanical strength of femur and tibia bones from hindlimb-unloaded rats fed an experimental synbiotic diet enriched with probiotics and fermentable fiber. Two calculated outputs for each sample were Young's modulus of elasticity and fracture stress. Bone major elements (calcium, magnesium, and phosphorous) were quantified using ICP-MS analysis. Hindlimb unloading was associated with a significant loss of strength in the femur, and with significant reductions in major bone elements. The synbiotic diet did not protect against these unloading effects. Tibia strength and major elements were not reduced by hindlimb unloading, as was

  3. Studies on the mechanisms underlying the transfer of calcium and phosphate from bone to blood

    Energy Technology Data Exchange (ETDEWEB)

    Brommage, Jr., Robert J. [Univ. of Rochester, NY (United States)

    1978-01-01

    The skeleton is recognized as a crucial organ in the minute-to-minute regulation of the blood levels of calcium and phosphate. The fluxes of calcium and phosphate to and from bone greatly exceed the entry and exit of these ions occurring in the intestine and kidneys. Parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3 are known to influence the transfer of calcium and phosphate from bone to blood. Three mechanisms have been proposed to explain the hormonal control of the calcium and phosphate effluxes from bone. The concept of a bone membrane maintaining a distinct bone extracellular fluid composition has led to the pump and pH gradient theories. An alternate solubilizer theory proposes that bone cells secrete a substance which increases the solubility of the bone mineral. The bone membrane concept was originally proposed to explain the presence of the apparent anomalously high concentrations of potassium in the bone extracellular fluid. However, the available evidence does not allow an unambiguous decision concerning the presence of a bone membrane. Calvarial lactate production was unaltered by 1,25-(OH)2D3 treatment and consequently 1,25-(OH)2D3 does not appear to promote the mobilization of bone mineral through a lactate-mediated pH gradient mechanism. 1,25-(OH)2D3 did increase the solubility of non-vital bone, clearly demonstrating that the solubilizer mechanism is at least partially responsible for the mobilization of bone mineral and the regulation of blood levels of calcium and phosphate. Vitamin D-deficient female rats fed a 0.2% calcium, 0.4% phosphorous diet and supplemented with daily injections of 0.75 pmole of 1,25-(OH)2D3 were shown to be capable of bearing young. When the injections of 1,25-(OH)2D3 were terminated at delivery, the dams and pups showed signs of vitamin D deficiency

  4. Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta.

    Science.gov (United States)

    Bart, Zachary R; Hammond, Max A; Wallace, Joseph M

    2014-08-01

    Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral, creating a brittle bone phenotype in animals. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained from µ-Computed Tomography and Raman spectroscopy indicate a smaller bone with reduced trabecular architecture and altered chemical composition. Decreased tissue material properties in oim/oim mice are likely driven by changes in collagen fibril structure, decreasing space available for mineral nucleation and growth, as supported by a reduction in mineral crystallinity. Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.

  5. In vivo measurement of mechanical properties of human long bone by using sonic sound

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, M. Jayed, E-mail: zed.hossain06@gmail.com; Rahman, M. Moshiur, E-mail: razib-121@yahoo.com; Alam, Morshed [Department of Mechanical Engineering, Bangladesh University of Engineering and Technology, Dhaka 1000 (Bangladesh)

    2016-07-12

    Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with the previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.

  6. [Ex Vivo Testing of Mechanical Properties of Canine Metacarpal/Metatarsal Bones after Simulated Implant Removal].

    Science.gov (United States)

    Srnec, R; Fedorová, P; Pěnčík, J; Vojtová, L; Sedlinská, M; Nečas, A

    2016-01-01

    PURPOSE OF THE STUDY In a long-term perspective, it is better to remove implants after fracture healing. However, subsequent full or excessive loading of an extremity may result in refracture, and the bone with holes after screw removal may present a site with predilection for this. The aim of the study was to find ways of how to decrease risk factors for refracture in such a case. This involved support to the mechanical properties of a bone during its remodelling until defects following implant removal are repaired, using a material tolerated by bone tissue and easy to apply. It also included an assessment of the mechanical properties of a bone after filling the holes in it with a newly developed biodegradable polymer-composite gel ("bone paste"). The composite also has a prospect of being used to repair bony defects produced by pathological processes. MATERIAL AND METHODS Experiments were carried out on intact weight-bearing small bones in dogs. A total of 27 specimens of metacarpal/metatarsal bones were used for ex vivo testing. They were divided into three groups: K1 (n = 9) control undamaged bones; K2 (n = 9) control bones with iatrogenic damage simulating holes left after cortical screw removal; EXP (n = 9) experimental specimens in which simulated holes in bone were filled with the biodegradable self-hardening composite. The bone specimens were subjected to three-point bending in the caudocranial direction by a force acting parallel to the direction of drilling in their middiaphyses. The value of maximum load achieved (N) and the corresponding value of a vertical displacement (mm) were recorded in each specimen, then compared and statistically evaluated. RESULTS On application of a maximum load (N), all bone specimens broke in the mid-part of their diaphyses. In group K1 the average maximum force of 595.6 ± 79.5 N was needed to break the bone; in group K2 it was 347.6 ± 58.6 N; and in group EXP it was 458.3 ± 102.7 N. The groups with damaged bones, K2 and

  7. [Levels of bone mineral matrix organization and the mechanisms determining parameters of its formation].

    Science.gov (United States)

    Avrunin, A S; Tikhilov, R M; Abolin, A B; Shcherbak, I G

    2005-01-01

    Authors suggest to regard bone mineral matrix as the four-level structure. The first level is represented by an internal structure of a mineral, the second--by mineral morphological structure, the third--by coplanar association of minerals, and the fourth--by macroassociation of minerals in a single complex inside each bone. The most probable mechanisms determining stability of reproduction of mineral matrix parameters on each of these levels are shown. As a result of their functioning, the variants of bone mineral matrix structures are formed that are the programmed reflection of specificity of the given site of organic structures.

  8. Physical activity and bone: The importance of the various mechanical stimuli for bone mineral density. A review

    Directory of Open Access Journals (Sweden)

    Bente Morseth

    2011-08-01

    Full Text Available Numerous studies have reported benefits of regular physical activity on bone mineral density (BMD. The effects of physical activity on BMD are primarily linked to the mechanisms of mechanical loading, but the understanding of the precise mechanism behind the association is incomplete. The aim of this paper was to review the main findings concerning sources and types of mechanical stimuli in relation to BMD. Mechanical forces that act on bone are generated from impact with the ground (ground-reaction forces and from skeletal muscle contractions (muscle forces or muscle-joint forces, but the relative importance of these two sources has not been elucidated. Both muscle-joint forces and gravitational forces seem to be able to induce bone adaptation independently, and there may be differences in the importance of loading sources at different skeletal sites. The nature of the stimuli is affected by the type, intensity, frequency, and duration of the activity. The activity should be dynamic, not static, and the magnitude and rate of the stimuli should be high. In accordance with this, cross-sectional studies report highest BMD in athletes of high-impact activities such as dancing, soccer, volleyball, basketball, squash, speed skating, gymnastics, hockey, and step-aerobics. Endurance activities such as orienteering, skiing, and triathlon seem to be beneficial to a lesser degree, whereas low-impact activities such as swimming and cycling are associated with lower BMD than controls. Both the intensity and frequency of the activity should be varied and increased beyond the habitual level. Duration of the activity seems to be less important, and a few loading cycles seem to be sufficient.

  9. Local Application of Growth Hormone to Enhance Osseointegration in Osteoporotic Bones: A Morphometric and Densitometric Study.

    Science.gov (United States)

    Martin-Monge, Elena; Tresguerres, Isabel F; Clemente, Celia; Tresguerres, Jesús Af

    The aim of this study was to assess the effect of local application of growth hormone on osseointegration of dental implants inserted in osteoporotic bones. Twenty female New Zealand rabbits were used in this study. Ten were ovariectomized and fed a low-calcium diet for 6 weeks, and the others remained intact. A titanium implant was inserted into each tibia, in both groups. In half of the rabbits, 2 IU of growth hormone was placed into the ostectomy prior to the implant insertion. Two weeks after implant surgery, all animals were sacrificed. Tibiae were dissected from soft tissues, and included in methacrylate to be studied under light microscopy. Bone-to-implant contact (BIC) and bone mineral density (BMD) were measured by morphometric and densitometric analysis, respectively. Multifactorial analysis of variance (ANOVA) was used for statistical evaluation. P growth hormone was able to increase the BIC in the ovariectomized group, with statistically significant differences with respect to the control group (P growth hormone at the moment of titanium implant insertion in rabbit tibiae significantly enhanced the BIC around titanium implants 15 days after the implantation in this experimental osteoporotic animal model, without affecting the BMD.

  10. Effect of concentrated growth factor combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis

    Directory of Open Access Journals (Sweden)

    Qiang Gao

    2017-10-01

    Full Text Available Objective: To study the effect of concentrated growth factor (CGF combined with guided bone regeneration on cell proliferation and bone resorption in patients with severe periodontitis. Methods: Patients with severe periodontitis who were treated in Stomatology Department of Shenmu Hospital between May 2014 and February 2017 were selected as the research subjects and randomly divided into two groups, surgery + CGF group received concentrated growth factor combined with guided bone regeneration, and pure surgery group received guided bone regeneration. The contents of inflammatory response, cell proliferation and bone resorption markers in gingival crevicular fluid were determined 1 week after treatment. Results: 1 week after treatment, HMGB1, ICAM1, E-selectin, Smac, FasL, Caspase-8, Caspase-9, Caspase-3, RANKL and NTX contents in gingival crevicular fluid of surgery + CGF group were significantly lower than those of pure surgery group while PD-L1, hBD-3, Wnt3a, BGP and OPG contents were significantly higher than those of pure surgery group. Conclusion: Concentrated growth factor combined with guided bone regeneration for severe periodontitis can inhibit inflammatory response, apoptosis and bone resorption, which is beneficial to the reconstruction of periodontal tissue.

  11. Study the bonding mechanism of binders on hydroxyapatite surface and mechanical properties for 3DP fabrication bone scaffolds.

    Science.gov (United States)

    Wei, Qinghua; Wang, Yanen; Li, Xinpei; Yang, Mingming; Chai, Weihong; Wang, Kai; zhang, Yingfeng

    2016-04-01

    In 3DP fabricating artificial bone scaffolds process, the interaction mechanism between binder and bioceramics power determines the microstructure and macro mechanical properties of Hydroxyapatite (HA) bone scaffold. In this study, we applied Molecular Dynamics (MD) methods to investigating the bonding mechanism and essence of binders on the HA crystallographic planes for 3DP fabrication bone scaffolds. The cohesive energy densities of binders and the binding energies, PCFs g(r), mechanical properties of binder/HA interaction models were analyzed through the MD simulation. Additionally, we prepared the HA bone scaffold specimens with different glues by 3DP additive manufacturing, and tested their mechanical properties by the electronic universal testing machine. The simulation results revealed that the relationship of the binding energies between binders and HA surface is consistent with the cohesive energy densities of binders, which is PAM/HA>PVA/HA>PVP/HA. The PCFs g(r) indicated that their interfacial interactions mainly attribute to the ionic bonds and hydrogen bonds which formed between the polar atoms, functional groups in binder polymer and the Ca, -OH in HA. The results of mechanical experiments verified the relationship of Young׳s modulus for three interaction models in simulation, which is PVA/HA>PAM/HA>PVP/HA. But the trend of compressive strength is PAM/HA>PVA/HA>PVP/HA, this is consistent with the binding energies of simulation. Therefore, the Young׳s modulus of bone scaffolds are limited by the Young׳s modulus of binders, and the compressive strength is mainly decided by the viscosity of binder. Finally, the major reasons for differences in mechanical properties between simulation and experiment were found, the space among HA pellets and the incomplete infiltration of glue were the main reasons influencing the mechanical properties of 3DP fabrication HA bone scaffolds. These results provide useful information in choosing binder for 3DP fabrication

  12. Effects of Neuropeptides and Mechanical Loading on Bone Cell Resorption in Vitro

    Directory of Open Access Journals (Sweden)

    Yeong-Min Yoo

    2014-04-01

    Full Text Available Neuropeptides such as vasoactive intestinal peptide (VIP and calcitonin gene-related peptide (CGRP are present in nerve fibers of bone tissues and have been suggested to potentially regulate bone remodeling. Oscillatory fluid flow (OFF-induced shear stress is a potent signal in mechanotransduction that is capable of regulating both anabolic and catabolic bone remodeling. However, the interaction between neuropeptides and mechanical induction in bone remodeling is poorly understood. In this study, we attempted to quantify the effects of combined neuropeptides and mechanical stimuli on mRNA and protein expression related to bone resorption. Neuropeptides (VIP or CGRP and/or OFF-induced shear stress were applied to MC3T3-E1 pre-osteoblastic cells and changes in receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL and osteoprotegerin (OPG mRNA and protein levels were quantified. Neuropeptides and OFF-induced shear stress similarly decreased RANKL and increased OPG levels compared to control. Changes were not further enhanced with combined neuropeptides and OFF-induced shear stress. These results suggest that neuropeptides CGRP and VIP have an important role in suppressing bone resorptive activities through RANKL/OPG pathway, similar to mechanical loading.

  13. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...... months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms/l after 4...

  14. Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.

    Science.gov (United States)

    Xing, Weirong; Govoni, Kristen E; Donahue, Leah Rae; Kesavan, Chandrasekhar; Wergedal, Jon; Long, Carlin; Bassett, J H Duncan; Gogakos, Apostolos; Wojcicka, Anna; Williams, Graham R; Mohan, Subburaman

    2012-05-01

    Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) (Tshr(-/-) and Duox2(-/-)), growth hormone (GH) (Ghrhr(lit/lit)), or both (Tshr(-/-); Ghrhr(lit/lit)), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition. Copyright © 2012 American Society for Bone and Mineral Research.

  15. Adaptation of BAp crystal orientation to stress distribution in rat mandible during bone growth

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, T; Fujitani, W; Ishimoto, T [Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1, Yamada-oka, Suita, Osaka 565-0871 (Japan); Umakoshi, Y [National Institute for Materials Science, 1-2-1, Sengen, Tsukuba, Ibaragi, 305-0471 (Japan)], E-mail: nakano@mat.eng.osaka-u.ac.jp

    2009-05-01

    Biological apatite (BAp) c-axis orientation strongly depends on stress distribution in vivo and tends to align along the principal stress direction in bones. Dentulous mandible is subjected to a complicated stress condition in vivo during chewing but few studies have been carried out on the BAp c-axis orientation; so the adaptation of BAp crystal orientation to stress distribution was examined in rat dentulous mandible during bone growth and mastication. Female SD rats 4 to 14 weeks old were prepared, and the bone mineral density (BMD) and BAp crystal orientation were analyzed in a cross-section of mandible across the first molar focusing on two positions: separated from and just under the tooth root on the same cross-section perpendicular to the mesiodistal axis. The degree of BAp orientation was analyzed by a microbeam X-ray diffractometer using Cu-K{alpha} radiation equipped with a detector of curved one-dimensional PSPC and two-dimensional PSPC in the reflection and transmission optics, respectively. BMD quickly increased during bone growth up to 14 weeks, although it was independent of the position from the tooth root. In contrast, BAp crystal orientation strongly depended on the age and the position from the tooth root, even in the same cross-section and direction, especially along the mesiodistal and the biting axes. With increased biting stress during bone growth, the degree of BAp orientation increased along the mesiodistal axis in a position separated from the tooth root more than that near the tooth root. In contrast, BAp preferential alignment clearly appeared along the biting axis near the tooth root. We conclude that BAp orientation rather than BMD sensitively adapts to local stress distribution, especially from the chewing stress in vivo in the mandible.

  16. Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits.

    Science.gov (United States)

    Cai, J; Li, W; Sun, T; Li, X; Luo, E; Jing, D

    2018-05-01

    The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/β-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/β-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. We reveal that PEMF improved bone architecture, mechanical properties, and

  17. A new method to produce macroporous Mg-phosphate bone growth substitutes

    Energy Technology Data Exchange (ETDEWEB)

    Babaie, Elham, E-mail: Elham.Babaie@rockets.utoledo.edu [Department of Biomedical Engineering, University of Toledo, Toledo, OH 43606 (United States); Lin, Boren [Department of Biomedical Engineering, University of Toledo, Toledo, OH 43606 (United States); Bhaduri, Sarit B. [Department of Mechanical, Industrial and Manufacturing Engineering, University of Toledo, Toledo, OH 43606 (United States); Department of Surgery (Dentistry), University of Toledo, Toledo, OH 43614 (United States)

    2017-06-01

    This paper is a sequel to our previous effort in developing Mg-phosphate orthopedic cements using amorphous Mg-phosphate (AMP) as the precursor. In this paper, we report a new real-time in situ technique to create macroporous bone growth substitute (BGS). The method uses biodegradable Mg-particles as the porogen. As opposed to the conventional wisdom of providing corrosion protection layers to biodegradable Mg-alloys, the present method uses the fast corrosion kinetics of Mg to create macropores in real time during the setting of the cement. An aqueous solution of PVA was used as the setting solution. Using this technique, a macroporous cement containing up to 91% porosity is obtained, as determined by pycnometry. Due to formation of H{sub 2} gas bubbles from corrosion of Mg, the cement becomes macroporous. The pore sizes as big as 760 μm were observed. The results of SBF soaking indicated change in crystallinity as confirmed via scanning electron microscopy (SEM) and X-ray diffraction (XRD). Our in vitro cytocompatibility evaluation also revealed that the macroporous bone growth substitute composed of bobierrite is cytocompatible and can improve gene expression. - Highlights: • We report a new real time, in situ technique to fabricate macroporous bone grafts. • Self-corroding Mg granules act as porogens. • Compositions containing AMP and PVA self-set within a reasonable time. • The final bone graft substitute showed promising biocompatibility. • The results provide important information on the porosity content and bioactivity.

  18. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... mass ex vivo.RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  19. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    M. Paknejad

    2012-01-01

    Full Text Available Objective: Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influ-ence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM on rabbit calvaria. Materials and Methods: Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Results: Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noti-ceable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Conclusion: Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the de-fects was not helpful.

  20. Evaluation of the Effect of Plasma Rich in Growth Factors (PRGF) on Bone Regeneration.

    Science.gov (United States)

    Paknejad, M; Shayesteh, Y Soleymani; Yaghobee, S; Shariat, S; Dehghan, M; Motahari, P

    2012-01-01

    Reconstruction methods are an essential prerequisite for functional rehabilitation of the stomatognathic system. Plasma rich in growth factors (PRGF) offers a new and potentially useful adjunct to bone substitute materials in bone reconstructive surgery. This study was carried out to investigate the influence of PRGF and fibrin membrane on regeneration of bony defects with and without deproteinized bovine bone mineral (DBBM) on rabbit calvaria. Twelve New Zealand white rabbits were included in this randomized, blinded, prospective study. Four equal 3.3×6.6 mm cranial bone defects were created and immediately grafted with DBBM, PRGF+DBBM, PRGF+fibrin membrane and no treatment as control. The defects were evaluated with histologic and histomorphometric analysis performed 4 and 8 weeks later. Adding PRGF to DBBM led to increased bone formation as compared with the control group in 4- and 8-week intervals. In DBBM and PRGF+fibrin membrane samples, no significant increase was seen compared to the control group. There was also a significant increase in the rate of biodegradation of DBBM particles with the addition of PRGF in the 8-week interval. Neither noticeable foreign body reaction nor any severe inflammation was seen in each of the specimens evaluated. Under the limitation of this study, adding PRGF to DBBM enhanced osteogenesis in rabbit calvarias. Applying autologous fibrin membrane in the defects was not helpful.

  1. Evaluation of ionizing radiation effects in bone tissue by FTIR spectroscopy and dynamic mechanical analysis

    International Nuclear Information System (INIS)

    Veloso, Marcelo N.; Santin, Stefany P.; Benetti, Carolina; Pereira, Thiago M.; Mattor, Monica B.; Politano, Rodolfo; Zezell, Denise M.

    2013-01-01

    In many medical practices the bone tissue exposure to ionizing radiation is necessary. However, this radiation can interact with bone tissue in a molecular level, causing chemical and mechanical changes related with the dose used. The aim of this study was verify the changes promoted by different doses of ionizing radiation in bone tissue using spectroscopy technique of Attenuate Total Reflectance - Fourier Transforms Infrared (ATR-FTIR) and dynamic mechanical analysis. Samples of bovine bone were irradiated using irradiator of Cobalt-60 with five different doses between 0.01 kGy, 0.1 kGy,1 kGy, 15 kGy and 75 kGy. To study the effects of ionizing irradiation on bone chemical structure the sub-bands of amide I and the crystallinity index were studied. The mechanical changes were evaluated using the elastic modulus and the damping value. To verify if the chemical changes and the bone mechanic characteristics were related, it was made one study about the correlation between the crystallinity index and the elastic modulus, between the sub-bands ratio and the damping value and between the sub-bands ratio and the elastic modulus. It was possible to evaluate the effects of different dose of ionizing radiation in bone tissue. With ATR-FTIR spectroscopy analysis, it was possible observe changes in the organic components and in the hydroxyapatite crystals organization. Changes were also observed in the mechanical properties. A good correlation between the techniques was found, however, it was not possible to establish a linear or exponential dependence between dose and effect. (author)

  2. Continuum damage mechanics method for fatigue growth of surface cracks

    International Nuclear Information System (INIS)

    Feng Xiqiao; He Shuyan

    1997-01-01

    With the background of leak-before-break (LBB) analysis of pressurized vessels and pipes in nuclear plants, the fatigue growth problem of either circumferential or longitudinal semi-elliptical surface cracks subjected to cyclic loading is studied by using a continuum damage mechanics method. The fatigue damage is described by a scalar damage variable. From the damage evolution equation at the crack tip, a crack growth equation similar to famous Paris' formula is derived, which shows the physical meaning of Paris' formula. Thereby, a continuum damage mechanics approach is developed to analyze the configuration evolution of surface cracks during fatigue growth

  3. Mechanical tension as a driver of connective tissue growth in vitro.

    Science.gov (United States)

    Wilson, Cameron J; Pearcy, Mark J; Epari, Devakara R

    2014-07-01

    We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in

  4. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

    Science.gov (United States)

    Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

    2016-02-01

    Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

  5. 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...... with docosahexaenoic acid (DHA) status and (ii) affected by fish oil supplementation, in adolescent boys. METHODS: Seventy-eight healthy, slightly overweight 13- to 15-y-old boys were randomly assigned to breads with DHA-rich fish oil (1.1 g/d n-3 LCPUFA) or control for 16 wk. Whole-body bone mineral content (BMC......), 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...

  6. The effect of growth factors for bone augmentation to enable dental implant placement: A systematic review

    Directory of Open Access Journals (Sweden)

    Kengo Shimono

    2010-02-01

    Differing levels and quantity of evidence were noted to be available for the growth factors evaluated, revealing that rhBMP-2, rhPDGF, and PRGF may stimulate local bone augmentation to various conditions. Especially the potential of rhBMP-2 is supportive. However, the confined number of investigators using these techniques and the low number of patient treatments reported in the literature, the generalizability of this approach is limited at this time.

  7. [The characteristics of chemical composition of content of unicameral bone cysts depending on their growth stage].

    Science.gov (United States)

    Stogov, M V; Luneva, S N; Mitrofanov, A I; Tkachuk, E A

    2012-11-01

    The article deals with the results of study of chemical composition of solitary cysts and blood serum of 27 patients. The results demonstrated that qualitative composition of f content of unicameral bone cysts is identical to chemical composition of blood serum. The results of analysis of total proteolysis activity and acid phosphatase activity in content of cysts can be used as criteria to determine the stage of cyst growth and to evaluate the effectiveness of applied treatment.

  8. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  9. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them

  10. Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

    Science.gov (United States)

    Joseph, Franklin; Ahmad, Aftab M; Ul-Haq, Mazhar; Durham, Brian H; Whittingham, Pauline; Fraser, William D; Vora, Jiten P

    2008-05-01

    Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate. IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age

  11. Plasma rich in growth factors and bone formation: a radiological and histomorphometric study in New Zealand rabbits

    Directory of Open Access Journals (Sweden)

    Francisco Molina-Miñano

    2009-09-01

    Full Text Available A radiographic and histomorphometric study was conducted on the influence of autologous plasma rich in growth factors (PRGF upon bone healing in surgically created defects in rabbits. Radiographically, bone regeneration was significantly greater with the use of PRGF after one month (p = 0.005, though no differences were recorded after the second month. In the histomorphometric analysis one month after surgery, the defects filled with autologous bone plus PRGF showed a greater percentage of neoformed bone (35.01 ± 5.31 than the control defects (22.90 ± 12.23, though the differences were not significant. Two months after surgery, the defects filled with autologous bone showed greater regeneration (46.04 ± 10.36% than the control defects (30.59 ± 5.69%, though the differences were not significant. The application of PRGF in the bone defects produced in New Zealand rabbits exerted a limited effect on local bone formation.

  12. Mechanism of growth retardation of the adenocarcinoma EO 771

    International Nuclear Information System (INIS)

    Bassukas, I.D.; Maurer-Schultze, B.

    1987-01-01

    Growth retardation of tumors has been predominantly described by an increase of the ''cell loss factor'' Φ. However, this cell loss factor alone merely reflects the growth deceleration without giving information on the mechanism that causes growth retardation. In the present study a quantitative analysis of the mechanism causing growth retardation of the adenocarcinoma EO 771 has been carried out by determining separately the components of the cell loss factor Φ, namely the cell production rate and the cell loss rate of the tumor cell population. For this purpose the alteration of the histology of the tumor (proportion of necrotic tumor tissue, tumor cell density) and the proliferative capacity of the tumor cell population as a function of the tumor size was studied by applying morphometric and cell kinetic methods. The results show that growth deceleration is due to a decrease of the cell production rate k p and a simultaneous increase of the cell rate k l . Both processes contribute to about the same extent to the growth deceleration of the tumor cell population. In early tumor growth deceleration is mainly due to a prolongation of the cycle time of the tumor cells, in later phases of tumor growth to an increasing probability of the tumor cells to decycle leading to a decrease of the growth fraction GF and an increase of the cell loss rate k l . (orig.)

  13. Effects of fatigue on microstructure and mechanical properties of bone organic matrix under compression

    International Nuclear Information System (INIS)

    Trębacz, Hanna; Zdunek, Artur; Cybulska, Justyna; Pieczywek, Piotr

    2013-01-01

    The aim of the study was to investigate whether a fatigue induced weakening of cortical bone was revealed in microstructure and mechanical competence of demineralized bone matrix. Two types of cortical bone samples (plexiform and Haversian) were use. Bone slabs from the midshaft of bovine femora were subjected to cyclical bending. Fatigued and adjacent control samples were cut into cubes and demineralized in ethylenediaminetetraacetic acid. Demineralized samples were either subjected to microscopic quantitative image analysis, or compressed to failure (in longitudinal or transverse direction) with a simultaneous analysis of acoustic emission (AE). In fatigued samples porosity of organic matrix and average area of pores have risen, along with a change in the pores shape. The effect of fatigue depended on the type of the bone, being more pronounced in the plexiform than in Haversian tissue. Demineralized bone matrix was anisotropic under compressive loads in both types of cortical structure. The main result of fatigue pretreatment on mechanical parameters was a significant decrease of ultimate strain in the transverse direction in plexiform samples. The decrease of strain in this group was accompanied by a considerable increase of the fraction of large pores and a significant change in AE energy.

  14. Beta Palmitate Improves Bone Length and Quality during Catch-Up Growth in Young Rats

    Directory of Open Access Journals (Sweden)

    Meytal Bar-Maisels

    2017-07-01

    Full Text Available Palmitic acid (PA is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the sn-2-position (termed beta palmitate, BPA and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to sn-1,3 PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with 1,3 PA or BPA-containing diets. We measured bone length, epiphyseal growth plate height (EGP, histology, bone quality (micro-CT and 3-point bending assay, and gene expression (Affymetrix. The BPA-containing diet improved most growth parameters: humeri length and EGP height were greater in the BPA-fed animals. Further analysis of the EGP revealed that the hypertrophic zone was significantly higher in the BPA group. In addition, Affymetrix analysis revealed that the diet affected the expression of several genes in the liver and EGP. Despite the very subtle difference between the diets and the short re-feeding period, we found a small but significant improvement in most growth parameters in the BPA-fed rats. This pre-clinical study may have important implications, especially for children with growth disorders and children with special nutritional needs.

  15. Prenatal nutritional manipulation by in ovo enrichment influences bone structure, composition, and mechanical properties.

    Science.gov (United States)

    Yair, R; Shahar, R; Uni, Z

    2013-06-01

    The objective of this study was to examine the effect of embryonic nutritional enrichment on the development and properties of broiler leg bones (tibia and femur) from the prenatal period until maturity. To accomplish the objective, 300 eggs were divided into 2 groups: a noninjected group (control) and a group injected in ovo with a solution containing minerals, vitamins, and carbohydrates (enriched). Tibia and femur from both legs were harvested from chicks on embryonic days 19 (E19) and 21 (E21) and d 3, 7, 14, 28, and 54 posthatch (n = 8). The bones were mechanically tested (stiffness, maximal load, and work to fracture) and scanned in a micro-computed tomography (μCT) scanner to examine the structural properties of the cortical [cortical area, medullary area, cortical thickness, and maximal moment of inertia (Imax)] and trabecular (bone volume percent, trabecular thickness, and trabecular number) areas. To examine bone mineralization, bone mineral density (BMD) of the cortical area was obtained from the μCT scans, and bones were analyzed for the ash and mineral content. The results showed improved mechanical properties of the enriched group between E19 and d 3 and on d 14 (P bones), greater femoral cortical area on d 3, and greater Imax of both bones on d 14 (P bone trabecular architecture were that the enriched group had greater bone volume percent and trabecular thickness in the tibia on d 7 and the femur on d 28 (P mineralization between E19 and d 54 showed improved mineralization in the enriched group on E19 whereas on d 3 and 7, the control group showed a mineralization advantage, and on d 28 and 54, the enriched group showed again greater mineralization (P bone properties pre- and postnatally and showed that avian embryos are a good model for studying the effect of embryonic nutrition on natal and postnatal development. Most importantly, the enrichment led to improved mechanical properties until d 14 (roughly third of the lifespan of the bird), a big

  16. Mechanical loading and how it affects bone cells: The role of the osteocyte cytoskeleton in maintaining our skeleton

    Directory of Open Access Journals (Sweden)

    J Klein-Nulend

    2012-09-01

    Full Text Available Lack of physical activity causes bone loss and fractures not only in elderly people, but also in bedridden patients or otherwise inactive youth. This is fast becoming one of the most serious healthcare problems in the world. Osteocytes, cells buried within our bones, stimulate bone formation in the presence of mechanical stimuli, as well as bone degradation in the absence of such stimuli. As yet, we do not fully comprehend how osteocytes sense mechanical stimuli, and only know a fraction of the whole range of molecules that osteocytes subsequently produce to regulate bone formation and degradation in response to mechanical stimuli. This dramatically hampers the design of bone loss prevention strategies. In this review we will focus on the first step in the cascade of events leading to adaptation of bone mass to mechanical loading, i.e., on how osteocytes are able to perceive mechanical stimuli placed on whole bones. We will place particular emphasis on the role of the osteocyte cytoskeleton in mechanosensing. Given the crucial importance of osteocytes in maintaining a proper resistance against bone fracture, greater knowledge of the molecular mechanisms that govern the adaptive response of osteocytes to mechanical stimuli may lead to the development of new strategies towards fracture prevention and enhanced bone healing.

  17. Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone

    DEFF Research Database (Denmark)

    Henriksen, S S; Ding, M; Vinther Juhl, M

    2011-01-01

    Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture....... Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength...

  18. Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment.

    Science.gov (United States)

    Bi, Xiaohong; Grafe, Ingo; Ding, Hao; Flores, Rene; Munivez, Elda; Jiang, Ming Ming; Dawson, Brian; Lee, Brendan; Ambrose, Catherine G

    2017-02-01

    Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap -/- ) and dominant (Col1a2 +/P.G610C ) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2 +/P.G610C femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in

  19. Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Vikjaer, D; Blom, S; Hjørting-Hansen, E

    1997-01-01

    The effect of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on bone healing was examined in calvarial defects in rabbits. Bicortical circular (critical size) defects were prepared in the calvarial bone of 16 rabbits. The defects were closed on the dural side and covered externally...

  20. The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

    DEFF Research Database (Denmark)

    Lange, Martin; Müller, Jørn; Svendsen, Ole Lander

    2005-01-01

    Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after...

  1. Physical activity programs for promoting bone mineralization and growth in preterm infants.

    Science.gov (United States)

    Schulzke, Sven M; Kaempfen, Siree; Trachsel, Daniel; Patole, Sanjay K

    2014-04-22

    Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth. The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium. The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants. Data collection, study selection, and data analysis were performed according to the methods of the CNRG. Eleven trials enrolling 324 preterm infants (gestational age 26 to 34 weeks) were included in this

  2. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    International Nuclear Information System (INIS)

    Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

    2015-01-01

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  3. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

    2015-03-27

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  4. Sequential growth factor application in bone marrow stromal cell ligament engineering.

    Science.gov (United States)

    Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

    2005-01-01

    In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

  5. A role for PERK in the mechanism underlying fluoride-induced bone turnover

    International Nuclear Information System (INIS)

    Sun, Fei; Li, Xining; Yang, Chen; Lv, Peng; Li, Guangsheng; Xu, Hui

    2014-01-01

    While it has been well-documented that excessive fluoride exposure caused the skeletal disease and osteoblasts played a critical role in the advanced skeletal fluorosis, the underlying mechanism that mediated these effects remain poorly understood. The present study was undertaken to examine the effect of fluoride on bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features of high bone turnover in fluoride-treated rats, which was supported by an increase of osteogenic and osteoclastogenic genes expression in different stages of fluoride exposure. The skeletal toxicity of fluoride was accompanied by activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). A novel finding of this study was that expression of PKR-like endoplasmic reticulum kinase (PERK) was the same trend with receptor activator for nuclear factor-κ B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2) was the same trend with Runt-related transcription factor 2 (Runx2) in bones of rats exposed to varied fluoride condition. Based on these data, we hypothesized that up-regulation of PERK probably played a role in mediating bone turnover induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was demonstrated through analysis of alkaline phosphatase (ALP) activity and mineralized nodules formation. Meantime, an increase of binding immunoglobulin protein (BiP) expression indicated the active ER stress in cells exposed to various dose of fluoride. Blocking PERK expression using siRNA showed the obvious decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells exposed to certain dose of fluoride that could positively stimulate osteoblastic viability. In conclusion these findings underscore the importance of PERK in modulating fluoride induced bone formation and bone resorption. Understanding the link between PERK and bone turnover could probe into the mechanism underlying different bone lesion of

  6. Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

    Science.gov (United States)

    Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

  7. Influence and evolution mechanism of different sharpness contact forms to mechanical property of cortical bone by nanoindentation

    Science.gov (United States)

    Sun, Xingdong; Guo, Yue; Li, Lijia; Liu, Zeyang; Wu, Di; Shi, Dong; Zhao, Hongwei; Zhang, Shizhong

    2018-03-01

    Based on different damage forms of various contact forms to bone, the mechanical response and mechanism were investigated by nanoindentation under different sharpness contact forms. For the purpose of simulating the different sharpness contact forms, two kinds of indenters were used in experiments and finite elements simulations. Through nanoindentation experiments, it was concluded that the residual depth of sharp indenter was bigger than that of blunt indenter with small penetration depth. However, the contrary law was obtained with bigger penetration depth. There was a turning point of transition from blunt tendency to sharp tendency. By calculation, it was concluded that the sharper the indenter was, the bigger the proportion of plastic energy in total energy was. Basically, results of finite elements simulation could correspond with the experimental conclusions. By the observation of FE-SEM, the surface of cortical bone compressed was more seriously directly below the blunt indenter than the lateral face. For the berkovich indenter, the surface of indentation compressed was less directly below the indenter, but seriously on three lateral faces. This research may provide some new references to the studies of bone fracture mechanism in different load patterns in the initial press-in stage and offer new explanation for bone trauma diagnosis in clinical treatment and criminal investigation.

  8. Influence and evolution mechanism of different sharpness contact forms to mechanical property of cortical bone by nanoindentation

    Directory of Open Access Journals (Sweden)

    Xingdong Sun

    2018-03-01

    Full Text Available Based on different damage forms of various contact forms to bone, the mechanical response and mechanism were investigated by nanoindentation under different sharpness contact forms. For the purpose of simulating the different sharpness contact forms, two kinds of indenters were used in experiments and finite elements simulations. Through nanoindentation experiments, it was concluded that the residual depth of sharp indenter was bigger than that of blunt indenter with small penetration depth. However, the contrary law was obtained with bigger penetration depth. There was a turning point of transition from blunt tendency to sharp tendency. By calculation, it was concluded that the sharper the indenter was, the bigger the proportion of plastic energy in total energy was. Basically, results of finite elements simulation could correspond with the experimental conclusions. By the observation of FE-SEM, the surface of cortical bone compressed was more seriously directly below the blunt indenter than the lateral face. For the berkovich indenter, the surface of indentation compressed was less directly below the indenter, but seriously on three lateral faces. This research may provide some new references to the studies of bone fracture mechanism in different load patterns in the initial press-in stage and offer new explanation for bone trauma diagnosis in clinical treatment and criminal investigation.

  9. Thermo-Mechanical Fatigue Crack Growth of RR1000.

    Science.gov (United States)

    Pretty, Christopher John; Whitaker, Mark Thomas; Williams, Steve John

    2017-01-04

    Non-isothermal conditions during flight cycles have long led to the requirement for thermo-mechanical fatigue (TMF) evaluation of aerospace materials. However, the increased temperatures within the gas turbine engine have meant that the requirements for TMF testing now extend to disc alloys along with blade materials. As such, fatigue crack growth rates are required to be evaluated under non-isothermal conditions along with the development of a detailed understanding of related failure mechanisms. In the current work, a TMF crack growth testing method has been developed utilising induction heating and direct current potential drop techniques for polycrystalline nickel-based superalloys, such as RR1000. Results have shown that in-phase (IP) testing produces accelerated crack growth rates compared with out-of-phase (OOP) due to increased temperature at peak stress and therefore increased time dependent crack growth. The ordering of the crack growth rates is supported by detailed fractographic analysis which shows intergranular crack growth in IP test specimens, and transgranular crack growth in 90° OOP and 180° OOP tests. Isothermal tests have also been carried out for comparison of crack growth rates at the point of peak stress in the TMF cycles.

  10. Thermo-Mechanical Fatigue Crack Growth of RR1000

    Directory of Open Access Journals (Sweden)

    Christopher John Pretty

    2017-01-01

    Full Text Available Non-isothermal conditions during flight cycles have long led to the requirement for thermo-mechanical fatigue (TMF evaluation of aerospace materials. However, the increased temperatures within the gas turbine engine have meant that the requirements for TMF testing now extend to disc alloys along with blade materials. As such, fatigue crack growth rates are required to be evaluated under non-isothermal conditions along with the development of a detailed understanding of related failure mechanisms. In the current work, a TMF crack growth testing method has been developed utilising induction heating and direct current potential drop techniques for polycrystalline nickel-based superalloys, such as RR1000. Results have shown that in-phase (IP testing produces accelerated crack growth rates compared with out-of-phase (OOP due to increased temperature at peak stress and therefore increased time dependent crack growth. The ordering of the crack growth rates is supported by detailed fractographic analysis which shows intergranular crack growth in IP test specimens, and transgranular crack growth in 90° OOP and 180° OOP tests. Isothermal tests have also been carried out for comparison of crack growth rates at the point of peak stress in the TMF cycles.

  11. Aging and loading rate effects on the mechanical behavior of equine bone

    Science.gov (United States)

    Kulin, Robb M.; Jiang, Fengchun; Vecchio, Kenneth S.

    2008-06-01

    Whether due to a sporting accident, high-speed impact, fall, or other catastrophic event, the majority of clinical bone fractures occur under dynamic loading conditions. However, although extensive research has been performed on the quasi-static fracture and mechanical behavior of bone to date, few high-quality studies on the fracture behavior of bone at high strain rates have been performed. Therefore, many questions remain regarding the material behavior, including not only the loading-rate-dependent response of bone, but also how this response varies with age. In this study, tests were performed on equine femoral bone taken post-mortem from donors 6 months to 28 years of age. Quasi-static and dynamic tests were performed to determine the fracture toughness and compressive mechanical behavior as a function of age at varying loading rates. Fracture paths were then analyzed using scanning confocal and scanning-electron microscopy techniques to assess the role of various microstructural features on toughening mechanisms.

  12. Mathematical model of mechanical testing of bone-implant (4.5 mm LCP construct

    Directory of Open Access Journals (Sweden)

    Lucie Urbanová

    2012-01-01

    Full Text Available The study deals with the possibility of substituting time- and material-demanding mechanical testing of a bone defect fixation by mathematical modelling. Based on the mechanical model, a mathematical model of bone-implant construct stabilizing experimental segmental femoral bone defect (segmental ostectomy in a miniature pig ex vivo model using 4.5 mm titanium LCP was created. It was subsequently computer-loaded by forces acting parallel to the long axis of the construct. By the effect of the acting forces the displacement vector sum of individual construct points occurred. The greatest displacement was noted in the end segments of the bone in close proximity to ostectomy and in the area of the empty central plate hole (without screw at the level of the segmental bone defect. By studying the equivalent von Mises stress σEQV on LCP as part of the tested construct we found that the greatest changes of stress occur in the place of the empty central plate hole. The distribution of this strain was relatively symmetrical along both sides of the hole. The exceeding of the yield stress value and irreversible plastic deformations in this segment of LCP occurred at the acting of the force of 360 N. These findings are in line with the character of damage of the same construct loaded during its mechanic testing. We succeeded in creating a mathematical model of the bone-implant construct which may be further used for computer modelling of real loading of similar constructs chosen for fixation of bone defects in both experimental and clinical practice.

  13. Selective LPCVD growth of graphene on patterned copper and its growth mechanism

    Science.gov (United States)

    Zhang, M.; Huang, B.-C.; Wang, Y.; Woo, J. C. S.

    2016-12-01

    Copper-catalyzed graphene low-pressure chemical-vapor deposition (LPCVD) growth has been regarded as a viable solution towards its integration to CMOS technology, and the wafer-bonding method provides a reliable alternative for transferring the selective graphene grown on a patterned metal film for IC manufacturing. In this paper, selective LPCVD graphene growth using patterned copper dots has been studied. The Raman spectra of grown films have demonstrated large dependence on the growth conditions. To explain the results, the growth mechanisms based on surface adsorption and copper-vapor-assisted growth are investigated by the comparison between the blanket copper films with/without the additional copper source. The copper vapor density is found to be critical for high-quality graphene growth. In addition, the copper-vapor-assisted growth is also evidenced by the carbon deposition on the SiO2 substrate of the patterned-copper-dot sample and chamber wall during graphene growth. This growth mechanism explains the correlation between the growth condition and Raman spectrum for films on copper dots. The study on the copper-catalyzed selective graphene growth on the hard substrate paves the way for the synthesis and integration of the 2D material in VLSI.

  14. Room temperature mushrooming of gallium wires and its growth mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, P.; Shen, L.W.; Ouyang, J.; Zhang, Y.M.; Wu, S.Q. [School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu (China); Sun, Z.M., E-mail: sunzhengming@gmail.com [School of Materials Science and Engineering, Southeast University, Nanjing 211189, Jiangsu (China); National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8569 (Japan)

    2015-01-15

    Highlights: • Fast spontaneous growth of Ga wires (∼200 nm/s) from a composite system of Cr{sub 2}GaC–Ga is reported. • The fact that Ga wires’ growth phenomena on the composite share most features with metals whiskers with metal/alloy substrates suggests the same mechanism highly likely operating with both systems. • Compelling evidences indicate that the popular stress-based mechanism developed in metal/alloy systems does not hold water in the Cr{sub 2}GaC–Ga composite system. • A new catalysis mechanism is proposed, in which the cleavage planes of Cr{sub 2}GaC grains act as a catalyst for the Ga wires growth. • The new findings in this composite system would lead a new route to address this old problem, and it might see significance in the electronics industry. On the other hand, it is likely to be harnessed to engineer a promising and facile route to prepare various metal wires in large scale. - Abstract: Spontaneous growth of Ga wires at high rate (∼200 nm/s) from a composite system of Cr{sub 2}GaC (a MAX phase) and Ga is presented. A Ga wire growth mechanism based on a catalysis model, which involves fractured Cr{sub 2}GaC grains as the catalyst, is proposed. Regarding the morphologies and the incubation time of the Ga wires, this system shares most features with metal/alloy substrates, such as tin and zinc, where the whiskering phenomenon has been well established and has resisted interpretation for 60+ years. The same growth mechanism is thus considered to operate across different substrates, including the composite one in this study. However, the experimental findings in this composite system oppose the popular stress-based mechanism for the whisker growth with metal/alloy substrates, and provide new sights on this phenomenon. In addition, compelling evidences strongly indicate that fractured Cr{sub 2}GaC grains produced by ball milling initiated the growth of Ga wires, like a ‘catalyst’, and the pristine Cr{sub 2}GaC grains do not

  15. Growth of ZnO nanostructures on Au-coated Si: Influence of growth temperature on growth mechanism and morphology

    DEFF Research Database (Denmark)

    Kumar, Rajendra; McGlynn, E.; Biswas, M.

    2008-01-01

    ZnO nanostructures were grown on Au-catalyzed Si silicon substrates using vapor phase transport at growth temperatures from 800 to 1150 degrees C. The sample location ensured a low Zn vapor supersaturation during growth. Nanostructures grown at 800 and 850 degrees C showed a faceted rodlike...... growth tended to dominate resulting in the formation of a porous, nanostructured morphology. In all cases growth was seen only on the Au-coated region. Our results show that the majority of the nanostructures grow via a vapor-solid mechanism at low growth temperatures with no evidence of Au nanoparticles...

  16. Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations.

    Science.gov (United States)

    Zuscik, Michael J; Ma, Lin; Buckley, Taylor; Puzas, J Edward; Drissi, Hicham; Schwarz, Edward M; O'Keefe, Regis J

    2007-09-01

    It has been established that skeletal growth is stunted in lead-exposed children. Because chondrogenesis is a seminal step during skeletal development, elucidating the impact of Pb on this process is the first step toward understanding the mechanism of Pb toxicity in the skeleton. The aim of this study was to test the hypothesis that Pb alters chondrogenic commitment of mesenchymal cells and to assess the effects of Pb on various signaling pathways. We assessed the influence of Pb on chondrogenesis in murine limb bud mesenchymal cells (MSCs) using nodule formation assays and gene analyses. The effects of Pb on transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signaling was studied using luciferase-based reporters and Western analyses, and luciferase-based assays were used to study cyclic adenosine monophosphate response element binding protein (CREB), beta-catenin, AP-1, and nuclear factor-kappa B (NF-kappaB) signaling. We also used an ectopic bone formation assay to determine how Pb affects chondrogenesis in vivo. Pb-exposed MSCs showed enhanced basal and TGF-beta/BMP induction of chondrogenesis, evidenced by enhanced nodule formation and up-regulation of Sox-9, type 2 collagen, and aggrecan, all key markers of chondrogenesis. We observed enhanced chondrogenesis during ectopic bone formation in mice preexposed to Pb via drinking water. In MSCs, Pb enhanced TGF-beta but inhibited BMP-2 signaling, as measured by luciferase reporter assays and Western analyses of Smad phosphorylation. Although Pb had no effect on basal CREB or Wnt/beta-catenin pathway activity, it induced NFkappaB signaling and inhibited AP-1 signaling. The in vitro and in vivo induction of chondrogenesis by Pb likely involves modulation and integration of multiple signaling pathways including TGF-beta, BMP, AP-1, and NFkappaB.

  17. Rentgeno-morphological manifestations of long bones growth breakage in case of acute injury of metaphysis and osteophysiolysis

    International Nuclear Information System (INIS)

    Radchenko, D.P.; Tkach, T.A.

    1982-01-01

    To study the effect of acute injury of metaphysis and osteoepiphysiolysis on the growth and formation of long tubular bones, as well as to develop X-ray characteristics of morphofunctional state of growth zone in dynamics 40 patients at the age of 1-18 were examined and experiments with 20 growing rabbits with metaphysis damages in isolated form and in combination with osteoepiphysiolysis were conducted. The certain regularity of deformation development and bone reduction, depending on damage degree was established

  18. Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate.

    Science.gov (United States)

    Choi, Hyeonhae; Choi, Yuri; Kim, Jisook; Bae, Jaeman; Roh, Jaesook

    2017-01-01

    We showed previously that caffeine adversely affects longitudinal bone growth and disrupts the histomorphometry of the growth plate during the pubertal growth spurt. However, little attention has been paid to the direct effects of caffeine on chondrocytes. Here, we investigated the direct effects of caffeine on chondrocytes of the growth plate in vivo and in vitro using a rapidly growing young rat model, and determined whether they were related to the adenosine receptor signaling pathway. A total of 15 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg -1  day -1 for 4 weeks. After sacrifice, the tibia processed for the analysis of the long bone growth and proliferation of chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine-fed animals showed decreases in matrix mineralization and proliferation rate of growth plate chondrocytes compared with the control. To evaluate whether caffeine directly affects chondrocyte proliferation and chondrogenic differentiation, primary rat chondrocytes were isolated from the growth plates and cultured in either the presence or absence of caffeine at concentrations of 0.1-1 mm, followed by determination of the cellular proliferation or expression profiles of cellular differentiation markers. Caffeine caused significant decreases in extracellular matrix production, mineralization, and alkaline phosphatase activity, accompanied with decreases in gene expression of the cartilage-specific matrix proteins such as aggrecan, type II collagen and type X. Our results clearly demonstrate that caffeine is capable of interfering with cartilage induction by directly inhibiting the synthetic activity and orderly expression of marker genes relevant to chondrocyte maturation. In addition, we found that the adenosine type 1 receptor signaling pathway may be partly involved in the detrimental effects of caffeine on chondrogenic

  19. Mechanism of Fatigue Crack Growth of Bridge Steel Structures

    Directory of Open Access Journals (Sweden)

    Zhu H.

    2016-12-01

    Full Text Available This study was carried out on the background of Sutong Bridge project based on fracture mechanics, aiming at analyzing the growth mechanism of fatigue cracks of a bridge under the load of vehicles. Stress intensity factor (SIF can be calculated by various methods. Three steel plates with different kinds of cracks were taken as the samples in this study. With the combination of finite element analysis software ABAQUS and the J integral method, SIF values of the samples were calculated. After that, the extended finite element method in the simulation of fatigue crack growth was introduced, and the simulation of crack growth paths under different external loads was analyzed. At last, we took a partial model from the Sutong Bridge and supposed its two dangerous parts already had fine cracks; then simulative vehicle load was added onto the U-rib to predict crack growth paths using the extended finite element method.

  20. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone.

    Science.gov (United States)

    Tomaszewska, E; Dobrowolski, P; Wydrych, J

    2012-10-01

    The potential effects of prenatal administration of dexamethasone (DEX) and postnatal treatment with 2-oxoglutaric acid (2-Ox) on postnatal development of connective tissue of farm animals were not examined experimentally. The aim of this study was to establish changes in morphological parameters of bone and articular and growth plate cartilages damaged by the prenatal action of DEX in piglets supplemented with 2-Ox. The 3 mg of DEX was administered by intramuscular route every second day from day 70 of pregnancy to parturition and then piglets were supplemented with 2-Ox during 35 days of postnatal life (0.4 g/kg body weight). The mechanical properties, BMD and BMC of bones, and histomorphometry of articular and growth plate cartilages were determined. Maternal treatment with DEX decreased the weight by 48%, BMD by 50% and BMC by 61% of the tibia in male piglets while such action of DEX in female piglets was not observed. DEX led to thinning of articular and growth plate cartilages and trabeculae thickness and reduced the serum GH concentration in male piglets. The administration of 2-Ox prevented the reduction of trabeculae thickness, the width of articular and growth plate cartilages in male piglets connected with higher growth hormone concentration compared with non-supplemented male piglets. The result showed that the presence of 2-Ox in the diet had a positive effect on the development of connective tissue in pigs during suckling and induced a complete recovery from bone and cartilage damage caused by prenatal DEX action.

  1. A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

    Science.gov (United States)

    Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

    2016-01-20

    A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

  2. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl Christian; Overgaard, Søren

    2011-01-01

    of 3 months without treatment. Group 3 was left untreated and served as controls. All sheep received a restricted diet with low calcium and phosphorus. At sacrifice, cortical bone samples from the femur midshaft of each sheep were harvested, micro-CT scanned and subjected to three-point bending...... and tensile strength testing. Bone collagen and mineral were determined. Cortical porosity was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Apparent density was significantly decreased in the glucocorticoid-2 compared with the glucocorticoid-1 group....... Collagen content was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Bone mineral content did not differ between the groups. Neither the three-point bending mechanical properties nor the tensile mechanical properties differed significantly between...

  3. Effect of Nanoparticle Incorporation and Surface Coating on Mechanical Properties of Bone Scaffolds: A Brief Review

    Directory of Open Access Journals (Sweden)

    Jesus Corona-Gomez

    2016-07-01

    Full Text Available Mechanical properties of a scaffold play an important role in its in vivo performance in bone tissue engineering, due to the fact that implanted scaffolds are typically subjected to stress including compression, tension, torsion, and shearing. Unfortunately, not all the materials used to fabricate scaffolds are strong enough to mimic native bones. Extensive research has been conducted in order to increase scaffold strength and mechanical performance by incorporating nanoparticles and/or coatings. An incredible improvement has been achieved; and some outstanding examples are the usage of nanodiamond, hydroxyapatite, bioactive glass particles, SiO2, MgO, and silver nanoparticles. This review paper aims to present the results, to summarize significant findings, and to give perspective for future work, which could be beneficial to future bone tissue engineering.

  4. Concise Review: Bone Marrow for the Treatment of Spinal Cord Injury: Mechanisms and Clinical Applications

    Science.gov (United States)

    Wright, Karina T; Masri, Wagih El; Osman, Aheed; Chowdhury, Joy; Johnson, William E B

    2011-01-01

    Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date. Stem Cells 2011;29:169–178 PMID:21732476

  5. Effects of epidermal growth factor on bone formation and resorption in vivo

    International Nuclear Information System (INIS)

    Marie, P.J.; Hott, M.; Perheentupa, J.

    1990-01-01

    The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double [3H]proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse

  6. Epitaxial growth mechanisms of graphene and effects of substrates

    OpenAIRE

    Özçelik, V. Ongun; Cahangirov, S.; Ciraci, S.

    2012-01-01

    The growth process of single layer graphene with and without substrate is investigated using ab initio, finite temperature molecular dynamic calculations within density functional theory. An understanding of the epitaxial graphene growth mechanisms in the atomic level is provided by exploring the transient stages which occur at the growing edges of graphene. These stages are formation and collapse of large carbon rings together with the formation and healing of Stone-Wales like pentagon-hepta...

  7. Distance from the growth plate and Its relation to the outcome of unicameral bone cyst treatment.

    Science.gov (United States)

    Haidar, Saadallah George; Culliford, David J; Gent, Edward David; Clarke, Nicholas M P

    2011-04-01

    Interventions to treat unicameral bone cysts vary. Nonetheless, regardless of the intervention modality, the outcome is not certain. The purpose of this study was to determine if the distance between the growth plate and the cyst can be used to predict the outcome of the treatment. Retrospectively, we assessed the outcome of 39 interventions in nineteen children that were performed between 1994 and 2003. Seventeen different modalities of treatment were employed. There were three female and sixteen male patients. The average age was 8 years. Nine cysts were in the greater trochanter area, three were in the femoral capital area and seven were in the proximal humerus. According to the cyst's distance from the growth plate, at the intervention time, there were 18 cases within less than 2 cm and 21 cases of more than 2 cm. Complete healing was achieved in 10 children (employing seven different modalities). In nine of them, the cysts were more than 2 cm away from the growth plate. In one child, the cyst was within less than 2 cm of the growth plate, however, treatment here involved epiphyseodesis. This study confirmed that, regardless of intervention modality, complete healing was not achievable in those cysts that are within less than 2 cm of an active growth plate. Complete healing was possible in those cysts that are more than 2 cm away from the growth plate. The 2-cm distance from the growth plate could be used as a predictor of treatment outcome of unicameral bone cysts.

  8. Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: a 7-year longitudinal study.

    Science.gov (United States)

    Xu, Leiting; Wang, Qin; Wang, Qingju; Lyytikäinen, Arja; Mikkola, Tuija; Völgyi, Eszter; Cheng, Shumei; Wiklund, Petri; Munukka, Eveliina; Nicholson, Patrick; Alén, Markku; Cheng, Sulin

    2011-09-01

    A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin-like growth factor 1 (IGF-1), estradiol (E(2) ), and testosterone (T) with peripubertal bone growth in a 7-year longitudinal study. Two-hundred and fifty-eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF-1, E(2) , and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF-1, E(2) , and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF-1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross-sectional area (mCSA). On the other hand, IGF-1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E(2) was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF-1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty. Copyright © 2011 American Society for Bone and Mineral Research.

  9. Immune mechanisms in Ehrlich ascites tumor growth in mice

    International Nuclear Information System (INIS)

    Marusic, M.

    1979-01-01

    Normal mice immunised with irradiated Ehrlich ascites tumor (EAT) cells rejected EAT challenge given 2 weeks later but T-cell-deficient thymectomised lethally irradiated, and bone-marrow-reconstituted (TIR) mice succumbed. However, when TIR mice were injected i.v. with thymus, lymph node, or spleen cells from normalsyngetic donors immediately following i.p. injection of irradiated EAT cells, they rejected the subsequent tumor challenge. This induction of immunity in TIR mice was shown to be T-cell dependent. Spleen cells from EAT- bearing mice given immediately after irradiated tumor cells were also able to promote rejection of EAT challenge in TIR mice. Spleen cells from EAT-immune mice inhibited EAT growth when admixed with tumor cells prior to i.p. injection into normal recipients, but had no effect on progressive tumor growth when given i.v. immediately after i.p. tumor injection. Immune serum inhibited i.p. EAT growth when given either i.p. or i.v. Whereas inhibition of EAT growth by admixed spleen cells was shown to be T-cell independent. The data indicate that T lymphocytes are required only in the induction phase of the immune reponse of mice against EAT, while the efferent phase of the response is accomplished by serum antibodies, perhaps through an interaction with host macrophages. (author)

  10. Selective Laser Melting: a regular unit cell approach for the manufacture of porous, titanium, bone in-growth constructs, suitable for orthopedic applications.

    Science.gov (United States)

    Mullen, Lewis; Stamp, Robin C; Brooks, Wesley K; Jones, Eric; Sutcliffe, Christopher J

    2009-05-01

    In this study, a novel porous titanium structure for the purpose of bone in-growth has been designed, manufactured and evaluated. The structure was produced by Selective Laser Melting (SLM); a rapid manufacturing process capable of producing highly intricate, functionally graded parts. The technique described utilizes an approach based on a defined regular unit cell to design and produce structures with a large range of both physical and mechanical properties. These properties can be tailored to suit specific requirements; in particular, functionally graded structures with bone in-growth surfaces exhibiting properties comparable to those of human bone have been manufactured. The structures were manufactured and characterized by unit cell size, strand diameter, porosity, and compression strength. They exhibited a porosity (10-95%) dependant compression strength (0.5-350 Mpa) comparable to the typical naturally occurring range. It is also demonstrated that optimized structures have been produced that possesses ideal qualities for bone in-growth applications and that these structures can be applied in the production of orthopedic devices. (c) 2008 Wiley Periodicals, Inc.

  11. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.

    Science.gov (United States)

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B

    2016-10-01

    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. © 2015 John Wiley & Sons Ltd.

  12. Mechanical model for filament buckling and growth by phase ordering.

    Science.gov (United States)

    Rey, Alejandro D; Abukhdeir, Nasser M

    2008-02-05

    A mechanical model of open filament shape and growth driven by phase ordering is formulated. For a given phase-ordering driving force, the model output is the filament shape evolution and the filament end-point kinematics. The linearized model for the slope of the filament is the Cahn-Hilliard model of spinodal decomposition, where the buckling corresponds to concentration fluctuations. Two modes are predicted: (i) sequential growth and buckling and (ii) simultaneous buckling and growth. The relation among the maximum buckling rate, filament tension, and matrix viscosity is given. These results contribute to ongoing work in smectic A filament buckling.

  13. Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

    Directory of Open Access Journals (Sweden)

    Vessella Robert L

    2006-01-01

    Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

  14. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  15. Transforming growth factor β induces bone marrow mesenchymal stem cell migration via noncanonical signals and N-cadherin.

    Science.gov (United States)

    Dubon, Maria Jose; Yu, Jinyeong; Choi, Sanghyuk; Park, Ki-Sook

    2018-01-01

    Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration, and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells. Inhibition of Rac1 by NSC23766 and Src by PP2 resulted in impaired TGF-β-mediated migration. These results suggested that the Smad-independent, noncanonical signals activated by TGF-β were necessary for migration. We also showed that N-cadherin-dependent intercellular interactions were required for TGF-β-mediated migration using functional inhibition of N-cadherin with EDTA treatment and a neutralizing antibody (GC-4 antibody) or siRNA-mediated knockdown of N-cadherin. However, N-cadherin knockdown did not affect the global activation of noncanonical signals in response to TGF-β. Therefore, these results suggested that the migration of BM-MSCs in response to TGF-β was mediated through N-cadherin and noncanonical TGF-β signals. © 2017 Wiley Periodicals, Inc.

  16. Premaxilla: an independent bone that can base therapeutics for middle third growth!

    Directory of Open Access Journals (Sweden)

    Mariana Trevizan

    Full Text Available ABSTRACT Premaxilla, in its early descriptions, had the participation of Goethe. In our face, in a certain period of growth and development processes, premaxilla is an independent and, then, a semi-independent bone to finally be totally integrated to the maxilla. Formation of the premaxilla acts as a stabilization element inside the facial skeleton comparable to the cornerstone of a Roman arch and is closely related to the development of human face and its abnormal growth with characteristic malformations. Until when the premaxillary-maxillary suture remains open and offers opportunities to orthopedically influence facial growth to exert influence over facial esthetics and function? Contact with preliminary results in 1183 skulls from anatomic museums at USP, Unicamp and Unifesp led us to question therapeutic perspectives and its clinical applicability.

  17. Premaxilla: an independent bone that can base therapeutics for middle third growth!

    Science.gov (United States)

    Trevizan, Mariana; Consolaro, Alberto

    2017-01-01

    Premaxilla, in its early descriptions, had the participation of Goethe. In our face, in a certain period of growth and development processes, premaxilla is an independent and, then, a semi-independent bone to finally be totally integrated to the maxilla. Formation of the premaxilla acts as a stabilization element inside the facial skeleton comparable to the cornerstone of a Roman arch and is closely related to the development of human face and its abnormal growth with characteristic malformations. Until when the premaxillary-maxillary suture remains open and offers opportunities to orthopedically influence facial growth to exert influence over facial esthetics and function? Contact with preliminary results in 1183 skulls from anatomic museums at USP, Unicamp and Unifesp led us to question therapeutic perspectives and its clinical applicability.

  18. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

    Directory of Open Access Journals (Sweden)

    Hye-Sun Yu

    2016-02-01

    Full Text Available Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations.

  19. Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk.

    Science.gov (United States)

    Nyman, Jeffry S; Granke, Mathilde; Singleton, Robert C; Pharr, George M

    2016-08-01

    Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown.

  20. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

    Science.gov (United States)

    Yu, Hye-Sun; Kim, Jung-Ju; Kim, Hae-Won; Lewis, Mark P; Wall, Ivan

    2016-01-01

    Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations. PMID:26977284

  1. Growth arrest line mimicking lymphoma involvement: The findings of {sup 99m}Tc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho [Hanyang University Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on {sup 99m}Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  2. Growth arrest line mimicking lymphoma involvement: The findings of 99mTc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho

    2016-01-01

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on 99m Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth

  3. Inter-dependent tissue growth and Turing patterning in a model for long bone development

    International Nuclear Information System (INIS)

    Tanaka, Simon; Iber, Dagmar

    2013-01-01

    The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We show that the reported IHH–PTCH1 interaction gives rise to a Schnakenberg-type Turing kinetics, and that inclusion of PTHrP is important to achieve robust patterning when coupling patterning and tissue dynamics. The model reproduces relevant spatiotemporal gene expression patterns, as well as a number of relevant mutant phenotypes. In summary, we propose that a ligand–receptor based Turing mechanism may control the emergence of patterns during long bone development, with PTHrP as an important mediator to confer patterning robustness when the sensitive Turing system is coupled to the dynamics of a growing and differentiating tissue. We have previously shown that ligand–receptor based Turing mechanisms can also result from BMP–receptor, SHH–receptor, and GDNF–receptor interactions, and that these reproduce the wildtype and mutant patterns during digit formation in limbs and branching morphogenesis in lung and kidneys. Receptor–ligand interactions may thus constitute a general mechanism to generate Turing patterns in nature. (paper)

  4. Inter-dependent tissue growth and Turing patterning in a model for long bone development

    Science.gov (United States)

    Tanaka, Simon; Iber, Dagmar

    2013-10-01

    The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We show that the reported IHH-PTCH1 interaction gives rise to a Schnakenberg-type Turing kinetics, and that inclusion of PTHrP is important to achieve robust patterning when coupling patterning and tissue dynamics. The model reproduces relevant spatiotemporal gene expression patterns, as well as a number of relevant mutant phenotypes. In summary, we propose that a ligand-receptor based Turing mechanism may control the emergence of patterns during long bone development, with PTHrP as an important mediator to confer patterning robustness when the sensitive Turing system is coupled to the dynamics of a growing and differentiating tissue. We have previously shown that ligand-receptor based Turing mechanisms can also result from BMP-receptor, SHH-receptor, and GDNF-receptor interactions, and that these reproduce the wildtype and mutant patterns during digit formation in limbs and branching morphogenesis in lung and kidneys. Receptor-ligand interactions may thus constitute a general mechanism to generate Turing patterns in nature.

  5. Expression of various growth factors for cell proliferation and cytodifferentiation during fracture repair of bone

    Directory of Open Access Journals (Sweden)

    M Fukuda

    2009-12-01

    Full Text Available We examined immunohistochemically the fracture repair process in rat tibial bone using antibodies to PCNA, BMP2, TGF-b 1,-2,-3, TGF-b R1,- R2, bFGF, bFGFR, PDGF, VEGF, and S-100. The peak level of cell proliferation as revealed by PCNA labelling appeared first in primitive mesenchymal cells and inflammatory cells at the fracture edges and neighboring periosteum at 2-days after fracture, followed by the peaks of periosteal primitive fibroblasts and chondroblasts, which appeared at fracture edges at 3- and 4-days after fracture, respectively. BMP2 was weakly positive in primitive mesenchymal cells, osteoblasts and chondroblasts. At 3-days post-fracture, periosteal osteoblasts produced osteoid tissue and callus with marrow spaces lined by osteoblasts and osteoclasts, and all primitive mesenchymal cells and osteoblasts were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. They were also positive for vascular growth factors bFGF, FGFR and PDGF, but negative for VEGF, and the peak of PCNA labelling of vascular endothelial cells in the marrow space was delayed to 4-days after fracture. Chondroblasts at fracture edges produced hypertrophic chondrocytes at 5-days after fracture and they were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. Primitive chondroblasts were positive for vascular growth factors VEGF as well as bFGF, FGFR, and the peak of PCNA labelling of vascular endothelial cells in the cartilage was at 5-days after fracture. Hypertrophic chondrocytes were also positive for these growth factors but negative for bFGF and bFGFR. S-100 protein-induced calcification was only positive on chondroblasts and hypertrophic chondrocytes. At 7-days after fracture, bone began to be formed from the cartilage at fracture edges, by a process similar to bone formation in the growth plate. Enchondral ossification established a bridge between both fracture edges and periosteal membranous ossification encompassed the fracture site like a sheath at 14- day after

  6. Thermo-Mechanical Fatigue Crack Growth of RR1000

    OpenAIRE

    Christopher John Pretty; Mark Thomas Whitaker; Steve John Williams

    2017-01-01

    Non-isothermal conditions during flight cycles have long led to the requirement for thermo-mechanical fatigue (TMF) evaluation of aerospace materials. However, the increased temperatures within the gas turbine engine have meant that the requirements for TMF testing now extend to disc alloys along with blade materials. As such, fatigue crack growth rates are required to be evaluated under non-isothermal conditions along with the development of a detailed understanding of related failure mechan...

  7. On some properties of bone functional adaptation phenomenon useful in mechanical design.

    Science.gov (United States)

    Nowak, Michał

    2010-01-01

    The paper discusses some unique properties of trabecular bone functional adaptation phenomenon, useful in mechanical design. On the basis of the biological process observations and the principle of constant strain energy density on the surface of the structure, the generic structural optimisation system has been developed. Such approach allows fulfilling mechanical theorem for the stiffest design, comprising the optimisations of size, shape and topology, using the concepts known from biomechanical studies. Also the biomimetic solution of multiple load problems is presented.

  8. Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head

    Science.gov (United States)

    Ma, Xiao-Wei; Cui, Da-Ping; Zhao, De-Wei

    2015-01-01

    Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head. PMID:26629044

  9. Mechanisms and applications of plant growth promoting rhizobacteria: Current perspective

    Directory of Open Access Journals (Sweden)

    Munees Ahemad

    2014-01-01

    Full Text Available Plant growth promoting rhizobacteria are the soil bacteria inhabiting around/on the root surface and are directly or indirectly involved in promoting plant growth and development via production and secretion of various regulatory chemicals in the vicinity of rhizosphere. Generally, plant growth promoting rhizobacteria facilitate the plant growth directly by either assisting in resource acquisition (nitrogen, phosphorus and essential minerals or modulating plant hormone levels, or indirectly by decreasing the inhibitory effects of various pathogens on plant growth and development in the forms of biocontrol agents. Various studies have documented the increased health and productivity of different plant species by the application of plant growth promoting rhizobacteria under both normal and stressed conditions. The plant-beneficial rhizobacteria may decrease the global dependence on hazardous agricultural chemicals which destabilize the agro-ecosystems. This review accentuates the perception of the rhizosphere and plant growth promoting rhizobacteria under the current perspectives. Further, explicit outlooks on the different mechanisms of rhizobacteria mediated plant growth promotion have been described in detail with the recent development and research. Finally, the latest paradigms of applicability of these beneficial rhizobacteria in different agro-ecosystems have been presented comprehensively under both normal and stress conditions to highlight the recent trends with the aim to develop future insights.

  10. Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children- a medical center experience.

    Science.gov (United States)

    Lin, Chien-Ming; Fan, Hueng-Chuen; Chao, Tsu-Yi; Chu, Der-Ming; Lai, Chi-Chieh; Wang, Chih-Chien; Chen, Shyi-Jou

    2016-05-03

    Children with longstanding use of antiepileptic drugs (AEDs) are susceptible to developing low bone mineral density and an increased fracture risk. However, the literature regarding the effects of AEDs on growth in epileptic children is limited. The aim of this study was to investigate the potential effects of valproate (VPA) and/or oxcarbazepine (OXC) therapy on growth velocity and bone metabolism. Seventy-three ambulatory children (40 boys and 33 girls) with epilepsy, aged between 1 and 18 years (mean age 9.8 ± 4.1 years), were evaluated for growth velocity before and for 1 year after VPA and/or OXC treatment. The bone resorption marker serum tartrate-resistant acid phosphatase 5b (TRAcP5b) and the bone formation marker serum bone-specific alkaline phosphatase (BAP) were measured post-AEDs therapy for 1 year. The difference in growth velocity (ΔHt) and body weight change (ΔWt) between pre- and post-AEDs treatment were -1.0 ± 2.8 cm/year (P effect of VPA and/or OXC therapy on dysregulation of bone metabolism might play a crucial role in physical growth.

  11. Quantifying mechanical force in axonal growth and guidance

    Directory of Open Access Journals (Sweden)

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  12. Growth Mechanism of Pumpkin-Shaped Vaterite Hierarchical Structures

    Science.gov (United States)

    Ma, Guobin; Xu, Yifei; Wang, Mu

    2015-03-01

    CaCO3-based biominerals possess sophisticated hierarchical structures and promising mechanical properties. Recent researches imply that vaterite may play an important role in formation of CaCO3-based biominerals. However, as a less common polymorph of CaCO3, the growth mechanism of vaterite remains not very clear. Here we report the growth of a pumpkin-shaped vaterite hierarchical structure with a six-fold symmetrical axis and lamellar microstructure. We demonstrate that the growth is controlled by supersaturation and the intrinsic crystallographic anisotropy of vaterite. For the scenario of high supersaturation, the nucleation rate is higher than the lateral extension rate, favoring the ``double-leaf'' spherulitic growth. Meanwhile, nucleation occurs preferentially in as determined by the crystalline structure of vaterite, modulating the grown products with a hexagonal symmetry. The results are beneficial for an in-depth understanding of the biomineralization of CaCO3. The growth mechanism may also be applicable to interpret the formation of similar hierarchical structures of other materials. The authors gratefully acknowledge the financial support from National Science Foundation of China (Grant Nos. 51172104 and 50972057) and National Key Basic Research Program of China (Grant No. 2010CB630705).

  13. A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

    Directory of Open Access Journals (Sweden)

    Eap S

    2015-02-01

    Full Text Available Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France; 2Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; 3Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain; 4CNRS (National Center for Scientific Research, ICS (Charles Sadron Institute, Strasbourg, France; 5Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain*These authors contributed equally to this workAbstract: New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone nanofibrous implant (from 700 µm to 1 cm thick was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII, 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7

  14. Periosteal PTHrP regulates cortical bone modeling during linear growth in mice.

    Science.gov (United States)

    Wang, Meina; VanHouten, Joshua N; Nasiri, Ali R; Tommasini, Steven M; Broadus, Arthur E

    2014-07-01

    The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone-related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal-diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx-Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound-like deformity. This was accompanied by a failure to induce receptor activator of NF-kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD-1 mice that was so moth-eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club-like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40-45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid-diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx-Cre-driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone. © 2014 Anatomical Society.

  15. Transforming Growth Factor Beta Signaling in Growth of Estrogen-Insensitive Metastatic Bone Lesions

    Science.gov (United States)

    2012-01-01

    osteolytic lesion areas. Corresponding 3D micro-CT images (bottom row). n=10 animals per treatment group. (B) Kaplan -meyer survival curve demonstrating...Gilks B, Yorida E, Cheang M, Turbin D, Gelmon K, Huntsman DG. Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3

  16. Highly deformable bones: unusual deformation mechanisms of seahorse armor.

    Science.gov (United States)

    Porter, Michael M; Novitskaya, Ekaterina; Castro-Ceseña, Ana Bertha; Meyers, Marc A; McKittrick, Joanna

    2013-06-01

    Multifunctional materials and devices found in nature serve as inspiration for advanced synthetic materials, structures and robotics. Here, we elucidate the architecture and unusual deformation mechanisms of seahorse tails that provide prehension as well as protection against predators. The seahorse tail is composed of subdermal bony plates arranged in articulating ring-like segments that overlap for controlled ventral bending and twisting. The bony plates are highly deformable materials designed to slide past one another and buckle when compressed. This complex plate and segment motion, along with the unique hardness distribution and structural hierarchy of each plate, provide seahorses with joint flexibility while shielding them against impact and crushing. Mimicking seahorse armor may lead to novel bio-inspired technologies, such as flexible armor, fracture-resistant structures or prehensile robotics. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  18. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  19. Mechanisms and pathways of growth failure in primordial dwarfism.

    Science.gov (United States)

    Klingseisen, Anna; Jackson, Andrew P

    2011-10-01

    The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

  20. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Growth Mechanism of Gold Nanorods in Binary Surfactant System

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo-Mi; Seo, Sun-Hwa; Joe, Ara; Shim, Kyu-Dong; Jang, Eue-Soon [Kumoh National Institute of Technology, Gumi (Korea, Republic of)

    2016-06-15

    In order to reveal the growth mechanism of gold nanorods (GNRs) in a binary surfactant system, we synthesized various GNRs by changing the concentration of the surfactants, AgNO{sub 3}, and HBr in the growth solution. We found that the benzyldime thylhexadecylammoniumchloride surfactant had weak interaction with the gold ions, but it could reduce the membrane fluidity. In addition, we could dramatically decrease the cetyltrimethylammonium bromide concentration required for GNR growth by adding an HBr solution. Notably, Ag{sup +} ions were necessary to break the symmetry of the seed crystals for GNR growth, but increasing the concentration of Ag{sup +} and Br{sup -} ions caused a decrease in the template size.

  2. Growth mechanism and magnon excitation in NiO nanowalls

    Directory of Open Access Journals (Sweden)

    Yang Chun

    2011-01-01

    Full Text Available Abstract The nanosized effects of short-range multimagnon excitation behavior and short-circuit diffusion in NiO nanowalls synthesized using the Ni grid thermal treatment method were observed. The energy dispersive spectroscopy mapping technique was used to characterize the growth mechanism, and confocal Raman scattering was used to probe the antiferromagnetic exchange energy J 2 between next-nearest-neighboring Ni ions in NiO nanowalls at various growth temperatures below the Neel temperature. This study shows that short spin correlation leads to an exponential dependence of the growth temperatures and the existence of nickel vacancies during the magnon excitation. Four-magnon configurations were determined from the scattering factor, revealing a lowest state and monotonic change with the growth temperature. PACS: 75.47.Lx; 61.82.Rx; 75.50.Tt; 74.25.nd; 72.10.Di

  3. Growth mechanism and magnon excitation in NiO nanowalls

    Science.gov (United States)

    2011-01-01

    The nanosized effects of short-range multimagnon excitation behavior and short-circuit diffusion in NiO nanowalls synthesized using the Ni grid thermal treatment method were observed. The energy dispersive spectroscopy mapping technique was used to characterize the growth mechanism, and confocal Raman scattering was used to probe the antiferromagnetic exchange energy J2 between next-nearest-neighboring Ni ions in NiO nanowalls at various growth temperatures below the Neel temperature. This study shows that short spin correlation leads to an exponential dependence of the growth temperatures and the existence of nickel vacancies during the magnon excitation. Four-magnon configurations were determined from the scattering factor, revealing a lowest state and monotonic change with the growth temperature. PACS: 75.47.Lx; 61.82.Rx; 75.50.Tt; 74.25.nd; 72.10.Di PMID:21824408

  4. Plant growth-promoting bacteria: mechanisms and applications.

    Science.gov (United States)

    Glick, Bernard R

    2012-01-01

    The worldwide increases in both environmental damage and human population pressure have the unfortunate consequence that global food production may soon become insufficient to feed all of the world's people. It is therefore essential that agricultural productivity be significantly increased within the next few decades. To this end, agricultural practice is moving toward a more sustainable and environmentally friendly approach. This includes both the increasing use of transgenic plants and plant growth-promoting bacteria as a part of mainstream agricultural practice. Here, a number of the mechanisms utilized by plant growth-promoting bacteria are discussed and considered. It is envisioned that in the not too distant future, plant growth-promoting bacteria (PGPB) will begin to replace the use of chemicals in agriculture, horticulture, silviculture, and environmental cleanup strategies. While there may not be one simple strategy that can effectively promote the growth of all plants under all conditions, some of the strategies that are discussed already show great promise.

  5. Bone growth, limb proportions and non-specific stress in archaeological populations from Croatia.

    Science.gov (United States)

    Pinhasi, R; Timpson, A; Thomas, M; Slaus, M

    2014-01-01

    The effect of environmental factors and, in particular, non-specific stress on the growth patterns of limbs and other body dimensions of children from past populations is not well understood. This study assesses whether growth of mediaeval and post-mediaeval children aged between 0-11.5 years from Adriatic (coastal) and continental Croatia varies by region and by the prevalence and type of non-specific stress. Dental ages were estimated using the Moorrees, Fanning and Hunt (MFH) scoring method. Growth of long bone diaphyses (femur, tibia, humerus, radius and ulna) was assessed by using a composite Z-score statistic (CZS). Clavicular length was measured as a proxy for upper trunk width, distal metaphyseal width of the femur was measured as a proxy for body mass and upper and lower intra-limb indices were calculated. Differences between sub-sets sampled by (a) region and (b) active vs healed non-specific stress indicators and (c) intra-limb indices were tested by Mann--Whitney U-tests and Analysis of Covariance (ANCOVA). Adriatic children attained larger dimensions-per-age than continental children. Children with healed stress lesions had larger dimensions-per-age than those with active lesions. No inter-regional difference was found in intra-limb indices. These findings highlight the complexity of growth patterns in past populations and indicate that variation in environmental conditions such as diet and differences in the nature of non-specific stress lesions both exert a significant effect on long bone growth.

  6. Effects of Growth Hormone/IGF-I and Exercise on Unloaded Bones

    Science.gov (United States)

    Harper, J. S.; Arnaud, S. B.; Gosselink, K. L.; Grindeland, R. E.

    1994-01-01

    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) in combination with exercise prevent muscle atrophy induced by unloading in the tail-suspension rat model for space flight (Gosselink et al, FASEB J 1994). This study evaluated the effects of these treatments on bone. Hypophysectomized rats were suspended (S) and treated with 1mg/kg/day CH plus IGF-I (H) or vehicle (Sal) daily by injection and exercised (Ex) by 3 climbs up a 1m ladder carrying a load equal to 30% the initial body weight (BW) 3x/day for 10 days. Tibial epiphysis (Epi) widths were measured by micrometry and femoral Bone Mineral Content (fBMC) in excised femurs by DEXA (Lunar DPX-L). Serum calcium (Ca) and phosphorus (Pi) were measured by COBAS Autoanalyzer (Roche Diag.). Ambulatory (Amb)-H treated rats showed growth rates of 6.6+-0.9 g/day, similar to S-H-Ex and higher than S-H (3.210.6, p less than 0.05) and S-Sal (-0.711.0, p less than 0.05). Epi widths were 10% lower in S-Sal, and S-Sal-Ex, and increased 100% in all H groups. fBMC was less in S than Amb, only when all S groups are compared to both Amb groups (p less than 0.03). H treatment increased fBMC (p less than 0.05) but reduced fBMC/100g BW in all H groups (p less than 0.001). The reduced density of H bone cannot be attributed to low circulating Ca. and Pi since they were higher in H than Sal (p less than 0.001). H treatment for 10 days in doses sufficient to support normal growth in BW failed to produce normal Epi widths or fBMC, even when combined with exercise. The suspension effect observed in Epi widths was not corrected by H or Ex alone, but was improved by H plus a This regimen. although effective in preventing muscle atrophy, failed to return bone measures, Epi widths and fBMC, to normal.

  7. Effect of growth hormone therapy and puberty on bone and body composition in children with idiopathic short stature and growth hormone deficiency.

    Science.gov (United States)

    Högler, Wolfgang; Briody, Julie; Moore, Bin; Lu, Pei Wen; Cowell, Christopher T

    2005-11-01

    The state of bone health and the effect of growth hormone (GH) therapy on bone and body composition in children with idiopathic short stature (ISS) are largely unknown. A direct role of GH deficiency (GHD) on bone density is controversial. Using dual-energy X-ray absorptiometry, this study measured total body bone mineral content (TB BMC), body composition, and volumetric bone mineral density (vBMD) at the lumbar spine (LS) and femoral neck (FN) in 77 children (aged 3-17 years) with ISS (n = 57) and GHD (n = 20). Fifty-five children (GHD = 13) receiving GH were followed over 24 months including measurement of bone turnover. At diagnosis, size-corrected TB BMC SDS was greater (P bone relation, as assessed by the BMC/lean mass (LTM) ratio SDS was not different between groups. During GH therapy, prepubertal GHD children gained more height (1.58 [0.9] SDS) and LTM (0.87 [0.63] SDS) compared to prepubertal ISS children (0.75 [0.27] and 0.17 [0.25] SDS, respectively). Percent body fat decreased in GHD (-5.94% [4.29]) but not in ISS children. Total body BMC accrual was less than predicted in all groups accompanied by an increase in bone turnover. Puberty led to the greatest absolute, but not relative, increments in weight, LTM, BMI, bone mass, and LSvBMD. Our results show that children with ISS and GHD differ in their response to GH therapy in anthropometry, body composition, and bone measures. Despite low vBMD values at diagnosis in both prepubertal groups, size-corrected regional or TB bone data were generally within the normal range and did not increase during GH therapy in GHD or ISS children. Growth hormone had great effects on the growth plate and body composition with subsequent gains in height, LTM, bone turnover, and bone mass accrual, but no benefit for volumetric bone density over 2 years.

  8. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl C; Overgaard, Søren

    2010-01-01

    The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone – Validation of large animal model for tissue engineering and biomaterial research Ming Ding,1* Carl Christian Danielsen,2 Søren Overgaard1 1Orthopaedic Research Laboratory......, Department of Orthopaedics and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark 2Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus C, Denmark Osteopenia in sheep has been successfully induced...... by glucocorticoid treatment and the changes in properties of cancellous bone were comparable with those observed in humans after long-term glucocorticoid treatment. However, the influence on cortical bone has not been thoroughly elucidated. This study aimed to investigate the influence of glucocorticoid on sheep...

  9. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Science.gov (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The interrelationship of porcine somatotropin administration and dietary phosphorus on growth performance and bone properties in developing gilts.

    Science.gov (United States)

    Weeden, T L; Nelssen, J L; Goodband, R D; Hansen, J A; Friesen, K G; Richert, B T

    1993-10-01

    Seventy-two gilts (initial weight = 57.9 kg) were used to determine the interrelationship of porcine somatotropin (pST) administration and dietary P on growth performance of finishing gilts (58 to 106 kg) and the effect on bone mechanical properties and mineralization for a 35-d postfinishing phase after withdrawal of pST administration. Gilts were injected daily with placebo (control) or 4 mg of pST and fed .4, .6, or .8% P in the finishing phase. Administration of pST increased ADG and G/F (P .18) on ADG, G/F, or ADFI for the overall finishing phase. When each block weight averaged 106 kg, half the gilts were slaughtered and the first rib, femur, and third and fourth metacarpals were collected. Stress, modulus of elasticity, and ash content of rib, femur, and metacarpals were reduced (P .22). The remaining 36 gilts were individually fed 1.8 kg/d of a common diet to assure a P intake of 22.8 g/d for the 35-d postfinishing phase. Gilts that received higher levels of dietary P during the finishing phase had increased (linear, P .4% P (10.3 g/d P) to maximize growth performance. However, a diet with .4% P (12.44 and 10.66 g/d P, control and pST-treated, respectively) was adequate for growth performance during the overall finishing phase (56 to 106 kg).(ABSTRACT TRUNCATED AT 400 WORDS)

  11. Anisotropic Growth of Otavite on Calcite: Implications for Heteroepitaxial Growth Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Riechers, Shawn L.; Kerisit, Sebastien N.

    2017-12-18

    Elucidating how cation intermixing can affect the mechanisms of heteroepitaxial growth in aqueous media has remained a challenging endeavor. Toward this goal, in situ atomic force microscopy was employed to image the heteroepitaxial growth of otavite (CdCO3) at the (10-14) surface of calcite (CaCO3) single crystals in static aqueous conditions. Heteroepitaxial growth proceeded via spreading of three-dimensional (3D) islands and two-dimensional (2D) atomic layers at low and high initial saturation levels, respectively. Experiments were carried out as a function of applied force and imaging mode thus enabling determination of growth mechanisms unaltered by imaging artifacts. This approach revealed the significant anisotropic nature of heteroepitaxial growth on calcite in both growth modes and its dependence on supersaturation, intermixing, and substrate topography. The 3D islands not only grew preferentially along the [42-1] direction relative to the [010] direction, resulting in rod-like surface precipitates, but also showed clear preference for growth from the island end rich in obtuse/obtuse kink sites. Pinning to step edges was observed to often reverse this tendency. In the 2D growth mode, the relative velocities of acute and obtuse steps were observed to switch between the first and second atomic layers. This phenomenon stemmed from the significant Cd-Ca intermixing in the first layer, despite bulk thermodynamics predicting the formation of almost pure otavite. Composition effects were also responsible for the inability of 3D islands to grow on 2D layers in cases where both modes were observed to occur simultaneously. Overall, the AFM images highlighted the effects of intermixing on heteroepitaxial growth, particularly how it can induce thickness-dependent growth mechanisms at the nanoscale.

  12. Mechanical test and fractal analysis on anisotropic fracture of cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Dagang [State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044 (China); College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Chen, Bin, E-mail: bchen@cqu.edu.cn [State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044 (China); College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Ye, Wei [College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Gou, Jihua [Department of Mechanical and Aerospace Engineering, University of Central Florida, Orlando, FL 32816 (United States); Fan, Jinghong [Division of Mechanical Engineering, Alfred University, Alfred, NY 14802 (United States)

    2015-12-01

    Highlights: • The mechanical properties of the cortical bone of fresh bovine femora along three different directions are tested through four-point bending experiments. • SEM observation shows that the roughness of the fracture surfaces of the three different directions of the bone are remarkably different. • The fractal dimensions of the different fracture surfaces of the bone are calculated by box-counting method in MATLAB. • The fracture energies of the different fracture directions are calculated based on their fractal models. - Abstract: The mechanical properties of the cortical bone of fresh bovine femora along three different directions are tested through four-point bending experiments. It is indicated that the fracture energy along the transversal direction of the bone is distinctly larger than those of the longitudinal and radial directions. The fracture surfaces of the three different directions are observed by scanning electron microscope (SEM). It is shown that the roughness of the fracture surface of the transversal direction is obviously larger than those of the fracture surfaces of the longitudinal and radial directions. It is also revealed that the osteons in the bone are perpendicular to the fracture surface of the transversal direction and parallel to the fracture surfaces of the longitudinal and radial directions. Based on these experimental results, the fractal dimensions of the fracture surfaces of different directions are calculated by box-counting method in MATLAB. The calculated results show that the fractal dimension of the fracture surface of the transversal direction is remarkably larger than those of the fracture surfaces of the longitudinal and radial directions. The fracture energies of different directions are also calculated based on their fractal models. It is denoted that the fracture energy of the transversal direction is remarkably larger than those of the longitudinal and radial directions. The calculated results are in

  13. Mechanical test and fractal analysis on anisotropic fracture of cortical bone

    International Nuclear Information System (INIS)

    Yin, Dagang; Chen, Bin; Ye, Wei; Gou, Jihua; Fan, Jinghong

    2015-01-01

    Highlights: • The mechanical properties of the cortical bone of fresh bovine femora along three different directions are tested through four-point bending experiments. • SEM observation shows that the roughness of the fracture surfaces of the three different directions of the bone are remarkably different. • The fractal dimensions of the different fracture surfaces of the bone are calculated by box-counting method in MATLAB. • The fracture energies of the different fracture directions are calculated based on their fractal models. - Abstract: The mechanical properties of the cortical bone of fresh bovine femora along three different directions are tested through four-point bending experiments. It is indicated that the fracture energy along the transversal direction of the bone is distinctly larger than those of the longitudinal and radial directions. The fracture surfaces of the three different directions are observed by scanning electron microscope (SEM). It is shown that the roughness of the fracture surface of the transversal direction is obviously larger than those of the fracture surfaces of the longitudinal and radial directions. It is also revealed that the osteons in the bone are perpendicular to the fracture surface of the transversal direction and parallel to the fracture surfaces of the longitudinal and radial directions. Based on these experimental results, the fractal dimensions of the fracture surfaces of different directions are calculated by box-counting method in MATLAB. The calculated results show that the fractal dimension of the fracture surface of the transversal direction is remarkably larger than those of the fracture surfaces of the longitudinal and radial directions. The fracture energies of different directions are also calculated based on their fractal models. It is denoted that the fracture energy of the transversal direction is remarkably larger than those of the longitudinal and radial directions. The calculated results are in

  14. Computationally-optimized bone mechanical modeling from high-resolution structural images.

    Directory of Open Access Journals (Sweden)

    Jeremy F Magland

    Full Text Available Image-based mechanical modeling of the complex micro-structure of human bone has shown promise as a non-invasive method for characterizing bone strength and fracture risk in vivo. In particular, elastic moduli obtained from image-derived micro-finite element (μFE simulations have been shown to correlate well with results obtained by mechanical testing of cadaveric bone. However, most existing large-scale finite-element simulation programs require significant computing resources, which hamper their use in common laboratory and clinical environments. In this work, we theoretically derive and computationally evaluate the resources needed to perform such simulations (in terms of computer memory and computation time, which are dependent on the number of finite elements in the image-derived bone model. A detailed description of our approach is provided, which is specifically optimized for μFE modeling of the complex three-dimensional architecture of trabecular bone. Our implementation includes domain decomposition for parallel computing, a novel stopping criterion, and a system for speeding up convergence by pre-iterating on coarser grids. The performance of the system is demonstrated on a dual quad-core Xeon 3.16 GHz CPUs equipped with 40 GB of RAM. Models of distal tibia derived from 3D in-vivo MR images in a patient comprising 200,000 elements required less than 30 seconds to converge (and 40 MB RAM. To illustrate the system's potential for large-scale μFE simulations, axial stiffness was estimated from high-resolution micro-CT images of a voxel array of 90 million elements comprising the human proximal femur in seven hours CPU time. In conclusion, the system described should enable image-based finite-element bone simulations in practical computation times on high-end desktop computers with applications to laboratory studies and clinical imaging.

  15. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay

    2015-01-01

    Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric...... turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity......./min/ 1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results: Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum...

  16. Morphological and mechanical characterization of chitosan-calcium phosphate composites for potential application as bone-graft substitutes

    Directory of Open Access Journals (Sweden)

    Guilherme Maia Mulder van de Graaf

    Full Text Available Introduction: Bone diseases, aging and traumas can cause bone loss and lead to bone defects. Treatment of bone defects is challenging, requiring chirurgical procedures. Bone grafts are widely used for bone replacement, but they are limited and expensive. Due to bone graft limitations, natural, semi-synthetic, synthetic and composite materials have been studied as potential bone-graft substitutes. Desirable characteristics of bone-graft substitutes are high osteoinductive and angiogenic potentials, biological safety, biodegradability, bone-like mechanical properties, and reasonable cost. Herein, we prepared and characterized potential bone-graft substitutes composed of calcium phosphate (CP - a component of natural bone, and chitosan (CS - a biocompatible biopolymer. Methods CP-CS composites were synthetized, molded, dried and characterized. The effect of drying temperatures (38 and 60 °C on the morphology, porosity and chemical composition of the composites was evaluated. As well, the effects of drying temperature and period of drying (3, 24, 48 and 72 hours on the mechanical properties - compressive strength, modulus of elasticity and relative deformation-of the demolded samples were investigated. Results Scanning electron microscopy and gas adsorption-desorption analyses of the CS-CP composites showed interconnected pores, indicating that the drying temperature played an important role on pores size and distribution. In addition, drying temperature have altered the color (brownish at 60 °C due to Maillard reaction and the chemical composition of the samples, confirmed by FTIR. Conclusion Particularly, prolonged period of drying have improved mechanical properties of the CS-CP composites dried at 38 °C, which can be designed according to the mechanical needs of the replaceable bone.

  17. Disp1 regulates growth of mammalian long bones through the control of Ihh distribution.

    Science.gov (United States)

    Tsiairis, Charisios D; McMahon, Andrew P

    2008-05-15

    Dispatched1 (Disp1) is required for the release of cholesterol modified hedgehog (Hh) proteins from producing cells. We investigated the role of Disp1 in Indian hedgehog (Ihh) signaling in the developing bone bypassing the lethality of the Disp1(C829F) allele at early somite stages through the supply of non-cholesterol modified Sonic hedgehog (N-Shh). The long bones that develop in the absence of wild-type Disp1, while clearly shorter, have a juxtaposition of proliferating and non-proliferating hypertrophic chondrocytes that is markedly more normal in organization than those of ihh null mutants. Direct analysis of Ihh trafficking in the target field demonstrates that Ihh is distributed well beyond Ihh expressing cells though the range of movement and signaling action is more restricted than in wild-type long bones. Consequently, a PTHrP-Ihh feedback loop is established, but over a shorter distance, reflecting the reduced range of Ihh movement. These analyses of the Disp1(C829F) mutation demonstrate that Disp1 is not absolutely required for the paracrine signaling role of Ihh in the skeleton. However, Disp1 is critical for the full extent of signaling within the chondrocyte target field and consequently the establishment of a normal skeletal growth plate.

  18. Evaluation of mandibular bone density to predict osteoporosis in adolescents with constitutional delayed growth

    International Nuclear Information System (INIS)

    Dural, Sema; Ozbek, Murat; Kanli, A.; Kanbur, Nuray O.; Derman, O.; Orhan, Kaan; Delilbasi, C.

    2005-01-01

    The aim of this study is to evaluate the correlation between constitutional delayed growth (CDG) and mandibular bone trabeculation as well as bone density on panoramic radiographs using a computer software program. Panoramic radiographs obtained from 25 patients with CDG and 25 healthy adolescents were evaluated for this study. Patients were selected from admission to Hacettepe University, Faculty of Medicine, Section of Adolescent Medicine in the first half of the year 2002. All panoramic radiographs were taken under standard conditions, and were randomized and then converted to digital images for density analysis using a scanner. The images were transferred to Osiris computer software program for the evaluation of bone density from 4 different regions on the mandible (right and left mandibular angle and condyle). The CDG group had higher values for the risk of osteoporosis considering the right (t=3.360, p=0.002) and the left condyle (t=3.620, p=0.001) (t-test for independent samples). It was also seen that the CDG group was again at higher risk in comparison to the control group when left mandibular angle values were measured (z= -2.447, p=0.014) (Mann Whitney - U test). We suggest that panoramic radiographs, which are transformed into digital format, can be valuable and economic tools for detecting the risk of osteoporosis in adolescents with CDG. (author)

  19. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats.

    Science.gov (United States)

    Grubbe, M-C; Thomsen, J S; Nyengaard, J R; Duruox, M; Brüel, A

    2014-12-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (aBMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, Pbone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse-induced loss of periosteal BFR/BS at the mid-femur and rectus femoris muscle mass.

  20. The effectiveness of the use of xenogeneic bone blocks mixed with autologous Concentrated Growth Factors (CGF in bone regeneration techniques: a case series

    Directory of Open Access Journals (Sweden)

    E. Gheno

    2014-06-01

    Full Text Available Aim: Different types of biomaterials and surgical techniques are currently used for the augmentation of atrophic ridges in view of implant supported restorations. The aim of this study was to clinically and histologically evaluate the combination of Concentrated Growth Factors (CGF and xenogeneic bone in vertical and/or horizontal ridge augmentation. Materials and methods: Seven patients (3 males and 4 females, who required oral implant and ridge augmentation surgery, were selected: 3 implants were placed during the surgery and 4 implants were inserted 4 months later, in order to allow complete graft integration. All implants were loaded after a 4-month healing time. The following parameters were assessed: a the capability of CGF to permeate the bone scaffold; b the degree of bone regeneration; c the clinical success rate. Results: The results obtained showed that: a with the used medical device porous bone scaffolds can be effectively permeated by the CGF; b the permeated grafting material resulted in effective bone regeneration, as confirmed by histomorphometric analysis; c all implants were successfully in function at the 12 months follow-up. Conclusion: This technique can be safely performed in the dental office under local anesthesia, so it can be considered a viable option in bone regeneration surgery.

  1. The Role of Mechanical Stimulation in Recovery of Bone Loss-High versus Low Magnitude and Frequency of Force.

    Science.gov (United States)

    Nagaraja, Mamta Patel; Jo, Hanjoong

    2014-04-02

    Musculoskeletal pathologies associated with decreased bone mass, including osteoporosis and disuse-induced bone loss, affect millions of Americans annually. Microgravity-induced bone loss presents a similar concern for astronauts during space missions. Many pharmaceutical treatments have slowed osteoporosis, and recent data shows promise for countermeasures for bone loss observed in astronauts. Additionally, high magnitude and low frequency impact such as running has been recognized to increase bone and muscle mass under normal but not microgravity conditions. However, a low magnitude and high frequency (LMHF) mechanical load experienced in activities such as postural control, has also been shown to be anabolic to bone. While several clinical trials have demonstrated that LMHF mechanical loading normalizes bone loss in vivo, the target tissues and cells of the mechanical load and underlying mechanisms mediating the responses are unknown. In this review, we provide an overview of bone adaptation under a variety of loading profiles and the potential for a low magnitude loading as a way to counteract bone loss as experienced by astronauts.

  2. The Role of Mechanical Stimulation in Recovery of Bone Loss—High versus Low Magnitude and Frequency of Force