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Bone Growth (bone + growth)
Kinds of Bone Growth Terms modified by Bone Growth Selected AbstractsCell proliferation and osteogenic differentiation of growing pig cranial suturesJOURNAL OF ANATOMY, Issue 3 2007Zongyang Sun Abstract Bone growth at the cranial sutures relies on proliferation of osteogenic progenitor cells and/or differentiation of osteoblasts. The current study was undertaken to assess these events in relation to suture growth and fusion. A total of 21 pigs, divided into three age groups (0.5,1.5 months, 3,4 months and 5,7 months), were used for immunohistochemical evaluation of cell proliferation (BrdU) and osteogenic differentiation (Cbfa1/Runx2) in the interfrontal and interparietal sutures. Proliferation and osteogenic differentiation were both more prominent near the bone fronts than in the central zone. With age, both proliferation and osteogenic differentiation diminished. Proliferation ceased on the endocranial (dura mater) side by the age of 3,4 months. Proliferation on the pericranial side was accompanied by active bone formation and initiation of suture fusion from this side. In conclusion, (1) decreased suture bone growth with age reflects decreased cell proliferation and probably also osteogenic differentiation, and (2) suture fusion occurs from the pericranial side where activity remains relatively high. [source] Technical note: Standardized and semiautomated Harris lines detectionAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2008S. Suter Abstract Arrest in long bone growth and the subsequent resumption of growth may be visible as radiopaque transverse lines in radiographs (Harris lines, HL; Harris, HA. 1933. Bone growth in health and disease. London: Oxford University Press). The assessment of individual age at occurrence of such lines, as part of paleopathological skeletal studies, is time-consuming and shows large intra- and interobserver variability. Thus, a standardized, automated detection algorithm would help to increase the validity of such paleopathological research. We present an image analysis application facilitating automatic detection of HL. On the basis of established age calculation methods, the individual age-at-formation can be automatically assessed with the tool presented. Additional user input to confirm the automatic result is possible via an intuitive graphical user interface. Automated detection of HL from digital radiographs of a sample of late Medieval Swiss tibiae was compared to the consensus of manual assessment by two blinded expert observers. The intra- and interobserver variability was high. The quality of the observer result improved when standardized detection criteria were defined and applied. The newly developed algorithm detected two-thirds of the HL that were identified as consensus lines between the observers. It was, however, necessary to validate the last one-third by manual editing. The lack of a large test series must be noted. The application is freely available for further testing by any interested researcher. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc. [source] Developmental toxicity of in ovo exposure to polychlorinated biphenyls: I. Immediate and subsequent effects on first-generation nestling American kestrels (Falco sparverius)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2003Kim Fernie Abstract We determined that in ovo exposure to polychlorinated biphenyls (PCBs) alters growth off first-generation nestlings during and one year after parental exposure. Captive American kestrels (Falco sparverius) laid eggs with environmentally relevant total PCB levels (34.1 ,g/g whole-egg wet wt) when fed PCB-spiked (Aroclor® 1248, 1254, and 1260) food (7 mg/kg body wt/d) for 100 d in 1998. In 1999, the same adults laid eggs with estimated total PCBs of 29.0 ,g/g. Nonsurviving PCB-exposed chicks were small (mass, bones) in 1998. Survivors showed a strong sex-specific growth response (mass, bones) compared to respective sex controls: Only female hatchlings were larger, and only male nestlings had longer feathers (1998); maximal growth and bone growth rates also differed (males were advanced, faster; females delayed, slower) (1999); and male nestlings fledged earlier and were smaller, while females were larger (1998, 1999). However, regardless of sex, PCB-exposed nestlings generally grew at faster rates in both years. In 1998, greater contaminant burdens and toxic equivalent concentrations in sibling eggs were associated with nestlings being lighter, having longer bones and feathers, and growing at faster rates (mass, bone) for females but slower rates (mass) for males. Both physiological-biochemical and behavioral changes are likely mechanisms. This study supports and expands on the Great Lakes embryo mortality, edema, and deformities syndrome: While PCB exposure alters nestling size, maximal growth and growth rates also change immediately, are sustained, and are sex specific. [source] Longitudinal development of equine conformation from weanling to age 3 years in the ThoroughbredEQUINE VETERINARY JOURNAL, Issue 7 2004T. M. ANDERSON Summary Reasons for performing study: There is little information available to define conformational changes with age using an objective but practical method of recording specific body measurements. Objective: To analyse conformation objectively in a population of racing Thoroughbreds and describe the changes from weanling to age 3 years. Methods: Annual photographs were taken over 4 years and conformation measurements made from photographs using specific reference points marked on the horses. Results: Correlation analysis revealed highly significant, moderate to strong relationships between long bone lengths and wither height for all ages. All long bone lengths showed moderate to strong relationships with each other for all ages. The front and rear pastern angles were significantly correlated with the angle of the dorsal surface of the front and rear hooves, respectively, for all. Wither height, croup height and length of neck topline, neck bottomline, scapula, humerus, radius and femur increased significantly from age 0,1 year and age 1,2 years. Hoof lengths (medial and lateral, right and left) grew significantly between the ages of 0 and 1 and 1 and 2 years, but decreased in length between age 2 and 3 years. Horses became more offset in the right limb between weanling and age 3 years, but the offset ratios did not change with age on the left limb. The angle of the scapula (I), shoulder and radiometacarpus significantly increased between all age groups (became more upright). The angle of the dorsal surface of the hooves (both front and hind) decreased significantly from ages 0 to 1 and 1 to 2 years, but showed no significant difference between ages 2 and 3 years. Conclusions: A strong relationship between long bone lengths and wither height for all ages supports the theory that horses are proportional. Longitudinal bone growth in the distal limb increased only 5,7% from weanling to age 3 years and is presumably completed prior to the yearling year. Several growth measures increased from ages 0 to 1 and 1 to 2 years, but did not increase from age 2,3 years; indicating that growth rate either showed or reached a plateau at this time. Potential relevance: This study provides objective information regarding conformation and skeletal growth in the Thoroughbred which can be utilised for selection and recognition of significant conformational abnormalities. [source] Responses of jawbone to pressure,GERODONTOLOGY, Issue 2 2004Gunnar E. Carlsson Objective:, To provide a literature review of bone resorption of edentulous jaws focusing on responses to pressure. Background:, After the extraction of all teeth in a jaw there is a continuous reduction of the residual ridge. The individual variation of bone resorption is great, and the aetiology is complex and not yet well understood. Materials and methods:, A search of the literature published up to May 2003 on bone resorption and pressure was performed using PubMed/Medline. Results:, Animal studies have demonstrated that excessive and constant pressure induces bone resorption. Recent experimental research has indicated that bone resorption is a pressure-regulated phenomenon with a lower threshold for continuous than for intermittent pressure. Clinical studies have suggested that residual ridge resorption is due more to the effects of denture wearing than to disuse atrophy. However, the results of leaving out dentures at night are not conclusive. Nor does the literature offer any strong evidence for the so-called combination syndrome, which has been described as a result of unfavourable loading. Clinical studies using multivariate analyses indicate that female gender and systemic factors may be of greater importance than oral and denture factors. Implant-supported prostheses have a bone preserving effect rather than the continuing resorption under complete dentures. Conclusions:, The best way to reduce bone resorption is to avoid total extraction, preserve a few teeth and fabricate overdentures. In edentulous jaws, placement of implant-supported prostheses will lead to less bone loss and may even promote bone growth. To increase our knowledge of residual ridge resorption extended experimental, clinical and statistical methods will be needed, preferably including collaboration between dental and medical researchers. [source] Treatment of osteopenia and osteoporosis in anorexia nervosa: A systematic review of the literatureINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2009Philip S. Mehler MD Abstract Objective: To systematically review the evidence supporting treatment of osteopenia and osteoporosis in patients with anorexia nervosa (AN). Data sources: We identified controlled clinical studies of interventions for low bone mass in AN via searches of MEDLINE; the Cochrane Library; EMBASE; PsycINFO; and cumulative index to nursing and allied health literature. Outcomes of interest were changes in bone mineral density and fracture incidence. Results: Six randomized controlled trials (RCTs) and two cohort trials examined five classes of medical therapy on bone mineral density outcomes. One RCT of bisphosphonates showed no benefit and a second flawed RCT showed some benefit; one RCT showed a benefit of insulin-like growth factor-I; none of the five trials evaluating estrogen therapy showed benefit. Discussion: Although patients with AN are often losing bone mass when they should be optimizing bone growth, there is no good evidence to guide medicinal interventions. Therefore, early detection and weight restoration are of utmost importance whereas ongoing trials define effective therapies. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source] Regional variability in secondary remodeling within long bone cortices of catarrhine primates: the influence of bone growth historyJOURNAL OF ANATOMY, Issue 3 2008Shannon C. McFarlin Abstract Secondary intracortical remodeling of bone varies considerably among and within vertebrate skeletons. Although prior research has shed important light on its biomechanical significance, factors accounting for this variability remain poorly understood. We examined regional patterning of secondary osteonal bone in an ontogenetic series of wild-collected primates, at the midshaft femur and humerus of Chlorocebus (Cercopithecus) aethiops (n = 32) and Hylobates lar (n = 28), and the midshaft femur of Pan troglodytes (n = 12). Our major objectives were: 1) to determine whether secondary osteonal bone exhibits significant regional patterning across inner, mid-cortical and outer circumferential cortical rings within cross-sections; and if so, 2) to consider the manner in which this regional patterning may reflect the influence of relative tissue age and other circumstances of bone growth. Using same field-of-view images of 100-µm-thick cross-sections acquired in brightfield and circularly polarized light microscopy, we quantified the percent area of secondary osteonal bone (%HAV) for whole cross-sections and across the three circumferential rings within cross-sections. We expected bone areas with inner and middle rings to exhibit higher %HAV than the outer cortical ring within cross-sections, the latter comprising tissues of more recent depositional history. Observations of primary bone microstructural development provided an additional context in which to evaluate regional patterning of intracortical remodeling. Results demonstrated significant regional variability in %HAV within all skeletal sites. As predicted,%HAV was usually lowest in the outer cortical ring within cross-sections. However, regional patterning across inner vs. mid-cortical rings showed a more variable pattern across taxa, age classes, and skeletal sites examined. Observations of primary bone microstructure revealed that the distribution of endosteally deposited bone had an important influence on the patterning of secondary osteonal bone across rings. Further, when present, endosteal compacted coarse cancellous bone always exhibited some evidence of intracortical remodeling, even in those skeletal sites exhibiting comparatively low %HAV overall. These results suggest that future studies should consider the local developmental origin of bone regions undergoing secondary remodeling later in life, for an improved understanding of the manner in which developmental and mechanical factors may interact to produce the taxonomic and intraskeletal patterning of secondary bone remodelling in adults. [source] Cell proliferation and osteogenic differentiation of growing pig cranial suturesJOURNAL OF ANATOMY, Issue 3 2007Zongyang Sun Abstract Bone growth at the cranial sutures relies on proliferation of osteogenic progenitor cells and/or differentiation of osteoblasts. The current study was undertaken to assess these events in relation to suture growth and fusion. A total of 21 pigs, divided into three age groups (0.5,1.5 months, 3,4 months and 5,7 months), were used for immunohistochemical evaluation of cell proliferation (BrdU) and osteogenic differentiation (Cbfa1/Runx2) in the interfrontal and interparietal sutures. Proliferation and osteogenic differentiation were both more prominent near the bone fronts than in the central zone. With age, both proliferation and osteogenic differentiation diminished. Proliferation ceased on the endocranial (dura mater) side by the age of 3,4 months. Proliferation on the pericranial side was accompanied by active bone formation and initiation of suture fusion from this side. In conclusion, (1) decreased suture bone growth with age reflects decreased cell proliferation and probably also osteogenic differentiation, and (2) suture fusion occurs from the pericranial side where activity remains relatively high. [source] Effect of Osteoblast-Targeted Expression of Bcl-2 in Bone: Differential Response in Male and Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005Alexander G Pantschenko Abstract Transgenic mice (Col2.3Bcl-2) with osteoblast-targeted human Bcl-2 expression were established. Phenotypically, these mice were smaller than their wildtype littermates and showed differential effects of the transgene on bone parameters and osteoblast activity dependent on sex. The net effect was an abrogation of sex differences normally observed in wildtype mice and an inhibition of bone loss with age. Ex vivo osteoblast cultures showed that the transgene had no effect on osteoblast proliferation, but decreased bone formation. Estrogen was shown to stimulate endogenous Bcl-2 message levels. These studies suggest a link between Bcl-2 and sex regulation of bone development and age-related bone loss. Introduction: Whereas Bcl-2 has been shown to be an important regulator of apoptosis in development, differentiation, and disease, its role in bone homeostasis and development is not well understood. We have previously showed that the induction of glucocorticoid-induced apoptosis occurred through a dose-dependent decrease in Bcl-2. Estrogen prevented glucocorticoid-induced osteoblast apoptosis in vivo and in vitro by preventing the decrease in Bcl-2 in osteoblasts. Therefore, Bcl-2 may be an important regulator of bone growth through mechanisms that control osteoblast longevity and function. Materials and Methods: Col2.3Bcl-2 mice were developed carrying a 2.3-kb region of the type I collagen promoter driving 1.8 kb of human Bcl-2 (hBcl-2). Tissue specific expression of hBcl-2 in immunoassays validated the transgenic animal model. Histomorphometry and DXA were performed. Proliferation, mineralization, and glucocorticoid-induced apoptosis were examined in ex vivo cultures of osteoblasts. The effect of estrogen on mouse Bcl-2 in ex vivo osteoblast cultures was assayed by RT-PCR and Q-PCR. Results and Conclusions: Two Col2.3Bcl-2 (tg/+) founder lines were established and appeared normal except that they were smaller than their nontransgenic wildtype (+/+) littermates at 1, 2, and 6 months of age, with the greatest differences at 2 months. Immunohistochemistry showed hBcl-2 in osteoblasts at the growth plate and cortical surfaces. Nontransgenic littermates were negative. Western blots revealed hBcl-2 only in type I collagen-expressing tissues. Histomorphometry of 2-month-old mice showed a significant decrease in tg/+ calvaria width with no significant differences in femoral trabecular area or cortical width compared with +/+. However, tg/+ males had significantly more trabecular bone than tg/+ females. Female +/+ mice showed increased bone turnover with elevated osteoblast and osteoclast parameters compared with +/+ males. Col2.3Bcl-2 mice did not show such significant differences between sexes. Male tg/+ mice had a 76.5 ± 1.5% increase in ObS/BS with no significant differences in bone formation rate (BFR) or mineral apposition rate (MAR) compared with male +/+ mice. Transgenic females had a significant 48.4 ± 0.1% and 20.1 ± 5.8% decrease in BFR and MAR, respectively, compared with +/+ females. Osteoclast and osteocyte parameters were unchanged. By 6 months, femurs from female and male +/+ mice had lost a significant amount of their percent of trabecular bone compared with 2-month-old mice. There was little to no change in femoral bone in the tg/+ mice with age. Ex vivo cultures of osteoblasts from +/+ and Col2.3Bcl-2 mice showed a decrease in mineralization, no effect on proliferation, and an inhibition of glucocorticoid-induced apoptosis in Col2.3Bcl-2 cultures. Estrogen was shown to increase mouse Bcl-2 transcript levels in osteoblast cultures of wildtype mice, supporting a role for Bcl-2 in the sex-related differences in bone phenotype regulated by estrogen. Therefore, Bcl-2 differentially affected bone phenotype in male and female transgenic mice, altered bone cell activity associated with sex-related differences, and decreased bone formation, suggesting that apoptosis is necessary for mineralization. In addition, Bcl-2 targeted to mature osteoblasts seemed to delay bone development, producing a smaller transgenic mouse compared with wildtype littermates. These studies suggest that expression of Bcl-2 in osteoblasts is important in regulating bone mass in development and in the normal aging process of bone. [source] Estrogen Receptor-, Inhibits Skeletal Growth and Has the Capacity to Mediate Growth Plate Fusion in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004AS Chagin Abstract To determine the long-term role of ER, in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Our results show that ER, inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. Introduction: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER),,/, and the ER,,/,,,/,, but not the ER,,/,, mouse models have clearly increased serum levels of estradiol. Materials and Methods: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Results: Young adult (4-month-old) ER,,/, mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER, inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER,,/, mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER,,/, mice, must be mediated through ER, because old ER,,/,,,/, mice displayed unchanged, unfused growth plates. Conclusions: Our results confirm that ER, is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER,, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice. [source] Increased Bone Formation in Mice Lacking Plasminogen Activators,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003E Daci Abstract Plasminogen activators tPA and uPA are involved in tissue remodeling, but their role in bone growth is undefined. Mice lacking tPA and uPA show increased bone formation and bone mass. The noncollagenous components of bone matrix are also increased, probably from defective degradation. This study underlines the importance of controlled bone matrix remodeling for normal endochondral ossification. Introduction: Proteolytic pathways are suggested to play a role in endochondral ossification. To elucidate the involvement of the plasminogen activators tPA and uPA in this process, we characterized the long bone phenotype in mice deficient in both tPA and uPA (tPA,/,:uPA,/,). Materials and Methods: Bones of 2- to 7-day-old tPA,/,:uPA,/, and wild-type (WT) mice were studied using bone histomorphometry, electron microscopy analysis, and biochemical assessment of bone matrix components. Cell-mediated degradation of metabolically labeled bone matrix, osteoblast proliferation, and osteoblast differentiation, both at the gene and protein level, were studied in vitro using cells derived from both genotypes. Results: Deficiency of the plasminogen activators led to elongation of the bones and to increased bone mass (25% more trabecular bone in the proximal tibial metaphysis), without altering the morphology of the growth plate. In addition, the composition of bone matrix was modified in plasminogen activator deficient mice, because an increased amount of proteoglycans (2×), osteocalcin (+45%), and fibronectin (+36%) was detected. Matrix degradation assays showed that plasminogen activators, by generating plasmin, participate in osteoblast-mediated degradation of the noncollagenous components of bone matrix. In addition, proliferation of primary osteoblasts derived from plasminogen activator-deficient mice was increased by 35%. Finally, osteoblast differentiation and formation of a mineralized bone matrix were enhanced in osteoblast cultures derived from tPA,/,:uPA,/, mice. Conclusions: The data presented indicate the importance of the plasminogen system in degradation of the noncollagenous components of bone matrix and suggest that the accumulation of these proteins in bone matrix,as occurs during plasminogen activator deficiency,may in turn stimulate osteoblast function, resulting in increased bone formation. [source] Effects of Liver-Derived Insulin-Like Growth Factor I on Bone Metabolism in Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002Klara Sjögren Abstract Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (LI-IGF-I,/,). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8,55) axial skeletal growth was decreased by 24% in the LI-IGF-I,/, mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I,/, mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I,/, mice. DNA microarray analysis of 30-week-old LI-IGF-I,/, and control mice indicated that only four genes were regulated in bone whereas ,40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice. [source] Is Leptin the Link Between Fat and Bone Mass?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2002Thierry Thomas Ph.D. Abstract Recently, leptin has emerged as a potential candidate responsible for protective effects of fat on bone tissue. However, it remains difficult to draw a clear picture of leptin effects on bone metabolism because published data are sometimes conflicting or apparently contradictory. Beyond differences in models or experimental procedures, it is tempting to hypothesize that leptin exerts dual effects depending on bone tissue, skeletal maturity, and/or signaling pathway. Early in life, leptin could stimulate bone growth and bone size through direct angiogenic and osteogenic effects on stromal precursor cells. Later, it may decrease bone remodeling in the mature skeleton, when trabecular bone turnover is high, by stimulating osteoprotegerin (OPG) expression. Leptin negative effects on bone formation effected through central nervous system pathway could counterbalance these peripheral and positive effects, the latter being predominant when the blood-brain barrier permeability decreases or the serum leptin level rises above a certain threshold. Thus, the sex-dependent specificity of the relationship between leptin and bone mineral density (BMD) in human studies could be, at least in part, caused by serum leptin levels that are two- to threefold higher in women than in men, independent of adiposity. Although these hypotheses remain highly speculative and require further investigations, existing studies consistently support the role of leptin as a link between fat and bone. [source] Control of chondrocyte gene expression by actin dynamics: a novel role of cholesterol/Ror-, signalling in endochondral bone growthJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Anita Woods Abstract Elucidating the signalling pathways that regulate chondrocyte differentiation, such as the actin cytoskeleton and Rho GTPases, during development is essential for understanding of pathological conditions of cartilage, such as chondrodysplasias and osteoarthritis. Manipulation of actin dynamics in tibia organ cultures isolated from E15.5 mice results in pronounced enhancement of endochondral bone growth and specific changes in growth plate architecture. Global changes in gene expression were examined of primary chondrocytes isolated from embryonic tibia, treated with the compounds cytochalasin D, jasplakinolide (actin modifiers) and the ROCK inhibitor Y27632. Cytochalasin D elicited the most pronounced response and induced many features of hypertrophic chondrocyte differentiation. Bioinformatics analyses of microarray data and expression validation by real-time PCR and immunohistochemistry resulted in the identification of the nuclear receptor retinoid related orphan receptor-, (Ror-,) as a novel putative regulator of chondrocyte hypertrophy. Expression of Ror-, target genes, (Lpl, fatty acid binding protein 4 [Fabp4], Cd36 and kruppel-like factor 5 [Klf15]) were induced during chondrocyte hypertrophy and by cytochalasin D and are cholesterol dependent. Stimulation of Ror-, by cholesterol results in increased bone growth and enlarged, rounded cells, a phenotype similar to chondrocyte hypertrophy and to the changes induced by cytochalasin D, while inhibition of cholesterol synthesis by lovastatin inhibits cytochalasin D induced bone growth. Additionally, we show that in a mouse model of cartilage specific (Col2-Cre) Rac1, inactivation results in increased Hif-1, (a regulator of Rora gene expression) and Ror-,+ cells within hypertrophic growth plates. We provide evidence that cholesterol signalling through increased Ror-, expression stimulates chondrocyte hypertrophy and partially mediates responses of cartilage to actin dynamics. [source] FGF and FGFR signaling in chondrodysplasias and craniosynostosisJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2005P.J. Marie Abstract The first experimental mouse model for FGF2 in bone dysplasia was made serendipitously by overexpression of FGF from a constitutive promoter. The results were not widely accepted, rightfully drew skepticism, and were difficult to publish; because of over 2,000 studies published on FGF-2 at the time (1993), only a few reported a role of FGF-2 in bone growth and differentiation. However, mapping of human dwarfisms to mutations of the FGFRs shortly, thereafter, made the case that bone growth and remodeling was a major physiological function for FGF. Subsequent production of numerous transgenic and targeted null mice for several genes in the bone growth and remodeling pathways have marvelously elucidated the role of FGFs and their interactions with other genes. Indeed, studies of the FGF pathway present one of the best success stories for use of experimental genetics in functionally parsing morphogenetic regulatory pathways. What remains largely unresolved is the pleiotropic nature of FGF-2. How does it accelerate growth in one cell then stimulate apoptosis or retard growth for another cell in the same type of tissue? Some of the answers may come through distinguishing the FGF-2 protein isoforms, made from alternative translation start sites, these appear to have substantially different functions. Although we have made substantial progress, there is still much to be learned regarding FGF-2 as a most complex, enigmatic protein. Studies of genetic models in mice and human FGFR mutations have provided strong evidence that FGFRs are important modulators of osteoblast function during membranous bone formation. However, there is some controversy regarding the effects of FGFR signaling in human and murine genetic models. Although significant progress has been made in our understanding of FGFR signaling, several questions remain concerning the signaling pathways involved in osteoblast regulation by activated FGFR. Additionally, little is known about the specific role of FGFR target genes involved in cranial bone formation. These issues need to be addressed in future in in vitro and in vivo approaches to better understand the molecular mechanisms of action of FGFR signaling in osteoblasts that result in anabolic effects in bone formation. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] CXCR4-independent rescue of the myeloproliferative defect of the gata1low myelofibrosis mouse model by Aplidin®,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Maria Verrucci The discovery of JAK2 mutations in Philadelphia-negative myeloproliferative neoplasms has prompted investigators to evaluate mutation-targeted treatments to restore hematopoietic cell functions in these diseases. However, the results of the first clinical trials with JAK2 inhibitors are not as promising as expected, prompting a search for additional drugable targets to treat these disorders. In this paper, we used the hypomorphic Gata1low mouse model of primary myelofibrosis (PMF), the most severe of these neoplasms, to test the hypothesis that defective marrow hemopoiesis and development of extramedullary hematopoiesis in myelofibrosis is due to insufficient p27Kip1 activity and is treatable by Aplidin®, a cyclic depsipeptide that activates p27Kip1 in several cancer cells. Aplidin® restored expression of Gata1 and p27Kip1 in Gata1low hematopoietic cells, proliferation of marrow progenitor cells in vitro and maturation of megakaryocytes in vivo (reducing TGF-,/VEGF levels released in the microenvironment by immature Gata1low megakaryocytes). Microvessel density, fibrosis, bone growth, and marrow cellularity were normal in Aplidin®-treated mice and extramedullary hematopoiesis did not develop in liver although CXCR4 expression in Gata1low progenitor cells remained low. These results indicate that Aplidin® effectively alters the natural history of myelofibrosis in Gata1low mice and suggest this drug as candidate for clinical evaluation in PMF. J. Cell. Physiol. 225: 490,499, 2010. © 2010 Wiley-Liss, Inc. [source] Mathematical modeling of appendicular bone growth in glaucous-winged gullsJOURNAL OF MORPHOLOGY, Issue 1 2009James L. Hayward Abstract Development of locomotor activity is crucial in tetrapods. In birds, this development leads to different functions for hindlimbs and forelimbs. The emergence of walking and flying as very different complex behavior patterns only weeks after hatching provides an interesting case study in animal development. We measured the diaphyseal lengths and midshaft diameters of three wing bones (humerus, ulna, and carpometacarpus) and three leg bones (femur, tibiotarsus, and tarsometatarsus) of 79 juvenile (ages 0,42 days) and 13 adult glaucous-winged gulls (Larus glaucescens), a semiprecocial species. From a suite of nine alternative mathematical models, we used information-theoretic criteria to determine the best model(s) for length and diameter of each bone as a function of age; that is, we determined the model(s) that obtained the best tradeoff between the minimized sum of squared residuals and the number of parameters used to fit the model. The Janoschek and Holling III models best described bone growth, with at least one of these models yielding an R2 , 0.94 for every dimension except tarsometatarsus diameter (R2 = 0.87). We used the best growth models to construct accurate allometric comparisons of the bones. Early maximal absolute growth rates characterize the humerus, femur, and tarsometatarsus, bones that assume adult-type support functions relatively early during juvenile development. Leg bone lengths exhibit more rapid but less sustained relative growth than wing bone lengths. Wing bone diameters are initially smaller than leg bone diameters, although this relationship is reversed by fledging. Wing bones and the femur approach adult length by fledging but continue to increase in diameter past fledging; the tibiotarsus and tarsometatarsus approach both adult length and diameter by fledging. In short, the pattern of bone growth in this semiprecocial species reflects the changing behavioral needs of the developing organism. J. Morphol., 2009. © 2008 Wiley-Liss, Inc. [source] Condylar resorption during active orthodontic treatment and subsequent therapy: report of a special case dealing with iatrogenic TMD possibly related to orthodontic treatmentJOURNAL OF ORAL REHABILITATION, Issue 5 2005Y. H. SHEN summary, A 28-year-old female underwent orthodontic treatment for approximately 22 months. During the later stages of this treatment, the patient reported right shoulder and neck-muscle pain. In addition, temporomandibular joint disorder (TMD) with a ,clicking' sound during mastication commenced 5 months prior to treatment completion. Specific medication to deal with these symptoms was suggested by medical specialists, as were some stress-relief methods, although the pain still progressed, and subsequent clinical and radiographical examinations were undertaken by another orthodontist. Right mandibular condylar resorption was observed from both the panorex and temporomandibular joint (TMJ) radiographs. No clinical signs of rheumatic disease were observed, although bruxism was noted. Following the termination of the orthodontic treatment by the second practitioner, the patient was treated with splint therapy 1 month subsequent to which, the previous symptoms of pain in the shoulder and neck, and the clicking sound during mastication had subsided. During the 14-month period of splint therapy and follow-up, new bone growth in the right condyle was observed from radiographs. [source] Collagen orientation in periosteum and perichondrium is aligned with preferential directions of tissue growthJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2008Jasper Foolen Abstract A feedback mechanism between different tissues in a growing bone is thought to determine the bone's morphogenesis. Cartilage growth strains the surrounding tissues, eliciting alterations of its matrix, which in turn, creates anisotropic stresses, guiding directionality of cartilage growth. The purpose of this study was to evaluate this hypothesis by determining whether collagen fiber directions in the perichondrium and periosteum align with the preferential directions of long bone growth. Tibiotarsi from chicken embryos across developmental stages were scanned using optical projection tomography (OPT) to assess preferential directions of growth at characteristic sites in perichondrium and periosteum. Quantified morphometric data were compared with two-photon laser-scanning microscopy images of the three-dimensional collagen network in these fibrous tissues. The diaphyseal periosteum contained longitudinally oriented collagen fibers that aligned with the preferential growth direction. Longitudinal growth at both metaphyses was twice the circumferential growth. This concurred with well-developed circumferential fibers, which covered and were partly interwoven with a dominant network of longitudinally oriented fibers in the outer layer of the perichondrium/periosteum at the metaphysis. Toward both articulations, the collagen network of the epiphyseal surface was randomly oriented, and growth was approximately biaxial. These findings support the hypothesis that the anisotropic architecture of the collagen network, detected in periosteum and perichondrium, concurs with the assessed growth directions. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1263,1268, 2008 [source] Free radical scavengers are more effective than indomethacin in the prevention of experimentally induced heterotopic ossificationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2007L.C. Vanden Bossche Abstract The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization,manipulation model was used to induce heterotopical ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N -acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:267,272, 2007 [source] Repair of rabbit segmental defects with the thrombin peptide, TP508JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Michael R. Sheller Abstract The synthetic peptide, TP508 (Chrysalin®), was delivered to rabbit segmental bone defects in biodegradable controlled-release PLGA microspheres to determine its potential efficacy for enhancing healing of non-critically and critically sized segmental defects. Non-critically sized radial defects were created in the forelimbs of New Zealand White rabbits, which were randomized into three treatment groups receiving 10, 50 and 100 ,g doses of TP508 in the right radius and control microspheres (without TP508) in the left radius. Torsional testing of the radii at six weeks showed a significant increase in ultimate torque, failure torque, ultimate energy, failure energy, and stiffness when treated with TP508 compared to controls (p < 0.01 for all measures). Thus, TP508 appeared to enhance or accelerate bone growth in these defects. In a second set of experiments, critically sized ulnar defects were created in the forelimbs of New Zealand White rabbits, which were randomized into two groups with each rabbit receiving microspheres with 100 or 200 ,g of TP508 into the right ulnar defect and control microspheres (without TP508) alone into the left ulnar defect. Bone healing was evaluated with plain radiographs, synchrotron-based microtomography, and mechanical testing. Radiographs of the rabbit limbs scored by three blinded, independent reviewers demonstrated a significantly higher degree of healing when treated with TP508 than their untreated control limbs (p < 0.05). Three-dimensional synchrotron tomography of a limited number of samples showed that the new bone in TP508-treated samples had a less porous surface appearance and open marrow spaces, suggesting progression of bone remodeling. Torsional testing of the ulnae at nine weeks showed a significant increase in maximum torque and failure energy when treated with TP508 compared to controls (p < 0.01 for both measures). These results suggest that TP508 in a controlled release delivery vehicle has the potential to enhance healing of segmental defects in both critically and non-critically sized defects. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] The Effect of a Constant Electrical Field on Osseointegration after Immediate Implantation in Dog Mandibles: A Preliminary StudyJOURNAL OF PROSTHODONTICS, Issue 5 2007Yadollah Soleymani Shayesteh DDS Purpose: The long time span between insertion of implants and functional rehabilitation often inconveniences patients. Accelerating bone growth around dental implants can shorten this time span. This in vivo study evaluated the effect of a constant electrical field on bone growth around dental implants. Materials and Methods: Four mongrel dogs were used in this study. Sixteen dental implants were placed immediately after extraction of the first premolar and molar teeth. A constant electrical field (CEF) generator was placed in the mucoperiostal pouch created from the subperiostral dissection under the inferior border of the dog's mandible and connected to the experiment side fixtures. CEF provided 3 V of electrical potential during osseointegration. Histologic sections were stained with hematoxylin,eosin and observed under light microscopy. The sections were analyzed histomorphometrically to calculate the amount of newly formed bone. Statistical analysis was performed with SPSS 11.0 computer software (,= 0.05). Results: At the end of the first stage of the osseointegration (90 days) CEF group sections showed enhanced growth of the trabeculae compared with the control group. Statistical analysis revealed significant differences between experimental and control groups. Bone contact ratio was statistically significant in the experimental group (p= 0.001). An increase in the local bone formation and bone contact ratio was observed with direct electrical stimulation of the implant and the bone area around the implant. Conclusion: Minimal direct electrical current, which can produce an electrical field around the implant, can increase the amount of bone formation and decrease the time of osseointegration. [source] Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in vivo longitudinal DCE-MRI studyNMR IN BIOMEDICINE, Issue 1 2010Marine Beaumont Abstract Tissue engineering is a promising technique for bone repair and can overcome the major drawbacks of conventional autogenous bone grafting. In this in vivo longitudinal study, we proposed a new tissue-engineering paradigm: inserting a biological soft-tissue construct within the bone defect to enhance angiogenesis for improved bone regeneration. The construct acts as a resorbable scaffold to support desired angiogenesis and cellular activity and as a vector of vascular endothelial growth factor, known to promote both vessel and bone growth. Dynamic contrast- enhanced magnetic resonance imaging was performed to investigate and characterize angiogenesis necessary for bone formation following the proposed paradigm of inserting a VEGF-impregnated tissue-engineered construct within the critical-sized calvarial defect in the membranous parietal bone of the rabbit. Results show that a model-free quantitative approach, the normalized initial area under the curve metric, provides sensitive and reproducible measures of vascularity that is consistent with known temporal evolution of angiogenesis during bone regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantitative radiographic changes in the mandible and the tibia in systemically loaded rats fed a low-calcium dietORAL DISEASES, Issue 5 2000Y Morimoto The combined effect of the duration of loaded physical exercise and the percentage of calcium intake on the mandible and tibia were studied in developing male rats. For the loaded exercise, rats ran on a treadmill at a rate of 12 m per min for either 1 or 2 h per day. A total of 54 4-week-old male Wistar rats were randomly assigned to one of six groups. After 4 weeks of the diet and loaded exercise, the rats were killed and their mandibles and tibia were removed. Each individual bone was assessed by radiography and the radiographs were then used for measurements of cortical thickness, bone length and bone width. All radiographic images were analyzed using a computer-based scanner image analysis system. In addition, we measured the dry weight both of the tibia and mandible. The results demonstrated that significant differences in cortical thickness, bone length, bone width, and bone weight, both of the tibia and the mandible, were detectable between the normal diet group and the low-calcium diet group. Among the normal diet groups, significant differences were found in cortical thickness, bone length, bone width, and bone weight of the tibia, whereas no significant differences in either cortical bone thickness, bone length or bone weight of the mandible were detected. In contrast, among the low-calcium diet groups, no significant differences were detected in cortical thickness, bone length, bone width or bone weight for either the tibia or the mandible. Our results suggested that systemic exercise, such as running, promote the linear dimensions and the cortical thickness of the tibia in response to local stimuli. Furthermore, sufficient calcium intake appears to be necessary to allow the effect of systemic exercise on tibial bone growth to occur. In contrast, systemic loaded exercise does not promote either bone growth or development of the mandible even under conditions of sufficient calcium intake. [source] Reversible skeletal changes after treatment with bevacizumab in a child with cutaneovisceral angiomatosis with thrombocytopenia syndromePEDIATRIC BLOOD & CANCER, Issue 3 2008Angela R. Smith MD Abstract Cutaneovisceral angiomatosis with thrombocytopenia (CAT) syndrome is a rare vascular disorder of the skin and gastrointestinal tract for which there is no standard treatment. We present a case in which a child with CAT syndrome was treated with bevacizumab, a vascular endothelial growth factor inhibitor, and subsequently developed asymptomatic metaphyseal bone lesions. Though not previously described as a side effect, we hypothesize that the use of bevacizumab in a child with active epiphyseal growth plates caused these radiographic lesions. Because of the potential for altered bone growth and metabolism, children receiving VEGF inhibitors should be monitored closely for bony toxicity. Pediatr Blood Cancer 2008;51:418,420. © 2008 Wiley-Liss, Inc. [source] Effect of a novel botanical agent Drynol Cibotin on human osteoblast cells and implications for osteoporosis: promotion of cell growth, calcium uptake and collagen productionPHYTOTHERAPY RESEARCH, Issue S2 2010Barbara Wegiel Abstract Osteoporosis is a widespread problem afflicting millions of people. Drynol Cibotinis is a newly developed proprietary botanical combination of eight botanicals including Angelica sinensis, Glycine max, Wild yam, Ligustrum lucidum, Astragalus membranaceus, Cuscuta chinensis, Psoraleae corylifoliae, and Drynaria fortune. Each of the botanicals has been used in traditional Chinese medicine to treat osteoporosis. The effect of Drynol Cibotinis, with the specific combination of these anti-osteoporosis botanicals for promoting bone growth, was examined in this study. The effects of Drynol Cibotin on cell growth, apoptosis, cell spreading, calcium uptake and production of bone matrix proteins Collagen I and Laminin B2 on human osteoblast cells were assessed by BrdU incorporation, TUNEL assay, cell staining, intracellular Ca2+ measurement and Western blot analysis. The results showed that Drynol Cibotin significantly increased cell proliferation and inhibited apoptosis in osteoblasts (P < 0.01). In addition, Drynol Cibotin was found to promote cell spreading and greatly increase calcium uptake both instantaneously and in the long term (P < 0.01). Furthermore, Drynol Cibotin significantly increased production of two key extracellular matrix proteins in bone cells: Collagen I and Laminin B2. These results indicate that Drynol Cibotin alone or in combination with amino acids and vitamins may have prophylactic potentials in osteoporosis. Copyright © 2009 John Wiley & Sons, Ltd. [source] Fluctuating and directional asymmetry in young human males: Effect of heavy working condition and socioeconomic status,AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2010Özener Abstract Many adverse environmental and genetic factors can affect stability of development during human growth. Although the level of fluctuating asymmetry (FA) may be influenced by environmental and genetic stress encountered during this period, directional asymmetry (DA) is largely attributable to differential mechanical loading during bone growth, for example, handedness. I assessed the effects of heavy working conditions and socioeconomic conditions on asymmetry levels in three groups of young human males: 1) individuals employed in the heavy industry sector (n = 104, mean age = 18.48 ± 0.61 years), 2) individuals who had the same socioeconomic status as the laborers (n = 102, mean age = 18.39 ± 0.58 years) but were not laborers, and 3) nonlaborers from the higher socioeconomic levels of society (n = 103, mean age = 18.43 ± 0.67). For all subjects, hand length, hand width, elbow width, wrist width, knee width, ankle width, foot length, foot width, ear length, and ear width were measured. All measurements of the upper extremities in the labor group appeared to exhibit DA; in the other two groups only hand measurements exhibited DA. According to analysis of FA, subjects living in poor conditions exhibited more FA than their nonlaborer peers living in better conditions. In addition, biomechanical pressures due to heavy working conditions of the labor group appeared to cause increased DA in the upper extremities: DA increased with an increase in the number of years working. Am J Phys Anthropol 143:13,20, 2010. © 2010 Wiley-Liss, Inc. [source] The effects of socioeconomic status on endochondral and appositional bone growth, and acquisition of cortical bone in children from 19th century Birmingham, EnglandAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009Simon Mays Abstract Endochondral growth, appositional growth, and acquisition of cortical bone thickness in the femur are investigated in subadult skeletons (N = 43, dental age range birth to 12 years) from the 19th -century AD burial site of St. Martin's churchyard, Birmingham, England. Endochondral growth is monitored using diaphyseal femoral length. Appositional growth is monitored using radiographic midshaft mediolateral width and acquisition of cortical bone using combined mediolateral cortical thickness measured at the midshaft from radiographs. The methodology involves plotting these variables against dental age. Growth is compared in children of differing socioeconomic status. Higher and lower status individuals are identified in the assemblage by their burial in brick vaults in the case of the former and in earth-cut graves in the case of the latter. The relationships between bone dimensions and dental age are described using a polynomial regression procedure, and analysis of regression residuals is used to evaluate differences in bone dimension-for-dental age between the two status groups. Results show that lower socioeconomic status individuals had lower cortical thickness-for-dental age than those of higher status. This was interpreted as likely reflecting poorer nutrition in the children of lower socioeconomic backgrounds. There was no patterning with respect to socioeconomic status in femur diaphyseal length or midshaft width. The results support the idea that, for skeletal populations, growth in cortical thickness may be a more sensitive indicator of adverse conditions in childhood than growth in bone length or width. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source] Masticatory loading and bone adaptation in the supraorbital torus of developing macaquesAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009K. Kupczik Abstract Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] Technical note: Standardized and semiautomated Harris lines detectionAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2008S. Suter Abstract Arrest in long bone growth and the subsequent resumption of growth may be visible as radiopaque transverse lines in radiographs (Harris lines, HL; Harris, HA. 1933. Bone growth in health and disease. London: Oxford University Press). The assessment of individual age at occurrence of such lines, as part of paleopathological skeletal studies, is time-consuming and shows large intra- and interobserver variability. Thus, a standardized, automated detection algorithm would help to increase the validity of such paleopathological research. We present an image analysis application facilitating automatic detection of HL. On the basis of established age calculation methods, the individual age-at-formation can be automatically assessed with the tool presented. Additional user input to confirm the automatic result is possible via an intuitive graphical user interface. Automated detection of HL from digital radiographs of a sample of late Medieval Swiss tibiae was compared to the consensus of manual assessment by two blinded expert observers. The intra- and interobserver variability was high. The quality of the observer result improved when standardized detection criteria were defined and applied. The newly developed algorithm detected two-thirds of the HL that were identified as consensus lines between the observers. It was, however, necessary to validate the last one-third by manual editing. The lack of a large test series must be noted. The application is freely available for further testing by any interested researcher. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||