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Skeletal Development (skeletal + development)
Kinds of Skeletal Development Selected AbstractsBone Dysplasias: An Atlas of Genetic Disorders of Skeletal Development, 2nd editionJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2005K Kozlowski No abstract is available for this article. [source] A Morphological Study of Skeletal Development in Turkey during the Pre-Hatching StageANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2009S. H. Atalgin Summary Skeletal chondrofication, ossification and growth of turkey embryos were investigated and analysed to enable assessment of the developmental status and evaluation of the experimental effects on skeletal development, skeletal mutations and development of cultured embryos. Ten embryos were prepared every 24 h from 8 to 28 days of incubation. The fixed embryos were cleared and stained in toto with Alcian blue & Alizarin red for cartilage and ossified components, respectively. Observation of the skeleton was performed under a stereoscopic microscopy, with special attention to the timing of chondrofication and ossification of the bones. The first occurrence of the primary ossification centres was observed in the femur, tibiotarsus, and the dentary and supra-angular of the mandible on the 12th day, followed immediately by the other long bones. Skeletal features of the skull were determined to show the latest appearance of cartilage and ossification. Hence, all elements of the hyolingual apparatus remained cartilaginous until hatching took place except for the ceratobranchial. Even though the vertebral column chondrified earlier as compared with the ribs and sternum, they ossified later. While chondrofication was present in all the regions of the vertebral column at the same time, ossification progressed from the cervical through caudal regions. The growth rate of the femur was eminently higher than that of the humerus with increase in time, particularly after the 20th day of incubation. This seems to be obviously natural because the eggs used in the study are from the broiler turkey, which gains giant muscle mass at a very short period; precocity is probably at the expense of the bones of the leg rather than those of the wing. [source] Targeted Expression of SHH Affects Chondrocyte Differentiation, Growth Plate Organization, and Sox9 Expression,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004Sara Tavella Abstract The role of Hedgehogs (Hh) in murine skeletal development was studied by overexpressing human Sonic Hedgehog (SHH) in chondrocytes of transgenic mice using the collagen II promoter/enhancer. Overexpression caused a lethal craniorachischisis with major alterations in long bones because of defects in chondrocyte differentiation. Introduction: Hedgehogs (Hhs) are a family of secreted polypeptides that play important roles in vertebrate development, controlling many critical steps of cell differentiation and patterning. Skeletal development is affected in many different ways by Hhs. Genetic defects and anomalies of Hhs signaling pathways cause severe abnormalities in the appendicular, axial, and cranial skeleton in man and other vertebrates. Materials and Methods: Genetic manipulation of mouse embryos was used to study in vivo the function of SHH in skeletal development. By DNA microinjection into pronuclei of fertilized oocytes, we have generated transgenic mice that express SHH specifically in chondrocytes using the cartilage-specific collagen II promoter/enhancer. Transgenic skeletal development was studied at different embryonic stages by histology. The expression pattern of specific chondrocyte molecules was studied by immunohistochemistry and in situ hybridization. Results: Transgenic mice died at birth with severe craniorachischisis and other skeletal defects in ribs, sternum, and long bones. Detailed analysis of long bones showed that chondrocyte differentiation was blocked at prehypertrophic stages, hindering endochondral ossification and trabecular bone formation, with specific defects in different limb segments. The growth plate was highly disorganized in the tibia and was completely absent in the femur and humerus, leading to skeletal elements entirely made of cartilage surrounded by a thin layer of bone. In this cartilage, chondrocytes maintained a columnar organization that was perpendicular to the bone longitudinal axis and directed toward its outer surface. The expression of SHH receptor, Patched-1 (Ptc1), was greatly increased in all cartilage, as well as the expression of parathyroid hormone-related protein (PTHrP) at the articular surface; while the expression of Indian Hedgehog (Ihh), another member of Hh family that controls the rate of chondrocyte maturation, was greatly reduced and restricted to the displaced chondrocyte columns. Transgenic mice also revealed the ability of SHH to upregulate the expression of Sox9, a major transcription factor implicated in chondrocyte-specific gene expression, in vivo and in vitro, acting through the proximal 6.8-kb-long Sox9 promoter. Conclusion: Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones. [source] Skeletal development of the Mexican spadefoot, Spea multiplicata (Anura: Pelobatidae)JOURNAL OF MORPHOLOGY, Issue 7 2006Barbara Banbury Abstract The larval chondrocranium of Spea multiplicata is described, as is the development and adult morphology of the skeleton. There are major modifications to the larval chondrocranium throughout development, including the presence of embryonic trabeculae in young tadpoles and significant reorganization of cartilaginous structures at metamorphosis. The first bone to ossify is the parasphenoid (Stage 35), followed by the presacral neural arches, ilium, and femur (Stage 36). By Stage 39, most of the postcranial elements have begun to ossify. Metamorphic climax is accomplished over three Gosner stages (39,41) and involves major modifications to the chondrocranium, as well as the appearance of three cranial elements (septomaxilla, nasal, and premaxilla). After metamorphosis, the exoccipital, vomer, dentary, angulosplenial, squamosal, pterygoid, sphenethmoid, ischium, and hyoid begin to ossify. The stapes, mentomeckelian, operculum, carpals, and tarsals do not appear until juvenile and adult stages. The development of the hyoid and cartilaginous condensations of the carpals and tarsals are described. In addition, phenotypic plasticity within the genus and the absence of a palatine (= neopalatine) bone are discussed. J. Morphol. © 2006 Wiley-Liss, Inc. [source] Skeletal development and deformities in cultured larval and juvenile seven-band grouper, Epinephelus septemfasciatus (Thunberg)AQUACULTURE RESEARCH, Issue 2 2007Naoki Nagano Abstract The seven-band grouper, Epinephelus septemfasciatus (Thunberg), is currently recognized as a potential new species for aquaculture in Japan. This study describes normal and abnormal skeletal development of the jaw and vertebrae in cultured larvae and early juveniles of E. septemfasciatus. The ontogenetic stages at which skeletal deformities of jaw and vertebra developed were also described for this species. Osteological observations were made using a clearing and staining method for larvae and soft X-ray photographs for juveniles. A high incidence of skeletal deformities was observed in the jaws and vertebral column during the larval and juvenile stages. Most of the jaw deformities were explained by an abnormal maxilla curvature. Jaw deformities were visually evident from flexion stage after ossification of the deformed elements. Deformities in the vertebral column (mostly lordosis) were observed from the post-larval stage and became more evident as growth proceeded. The lordosis generally occurred on the positions of the 8,11th vertebra. These types of deformities are compared with those of other species, and possible causative factors of the skeletal deformities are discussed. [source] E2f6 and Bmi1 cooperate in axial skeletal developmentDEVELOPMENTAL DYNAMICS, Issue 5 2008Maria Courel Abstract Bmi1 is a Polycomb Group protein that functions as a component of Polycomb Repressive Complex 1 (PRC1) to control axial skeleton development through Hox gene repression. Bmi1 also represses transcription of the Ink4a-Arf locus and is consequently required to maintain the proliferative and self-renewal properties of hematopoietic and neural stem cells. Previously, one E2F family member, E2F6, has been shown to interact with Bmi1 and other known PRC1 components. However, the biological relevance of this interaction is unknown. In this study, we use mouse models to investigate the interplay between E2F6 and Bmi1. This analysis shows that E2f6 and Bmi1 cooperate in the regulation of Hox genes, and consequently axial skeleton development, but not in the repression of the Ink4a-Arf locus. These findings underscore the significance of the E2F6,Bmi1 interaction in vivo and suggest that the Hox and Ink4a-Arf loci are regulated by somewhat different mechanisms. Developmental Dynamics 237:1232-1242, 2008. © 2008 Wiley-Liss, Inc. [source] Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal developmentDEVELOPMENTAL DYNAMICS, Issue 2 2008Andreas Ratzka Abstract Modification of the sulfation pattern of heparan sulfate (HS) during organ development is thought to regulate binding and signal transduction of several growth factors. The secreted sulfatases, Sulf1 and Sulf2, desulfate HS on 6-O-positions extracellularly. We show that both sulfatases are expressed in overlapping patterns during embryonic skeletal development. Analysis of compound mutants of Sulf1 and Sulf2 derived from gene trap insertions and targeted null alleles revealed subtle but distinct skeletal malformations including reduced bone length, premature vertebrae ossification and fusions of sternebrae and tail vertebrae. Molecular analysis of endochondral ossification points to a function of Sulf1 and Sulf2 in delaying the differentiation of endochondral bones. Penetrance and severity of the phenotype increased with reduced numbers of functional alleles indicating redundant functions of both sulfatases. The mild skeletal phenotype of double mutants suggests a role for extracellular modification of 6-O-sulfation in fine-tuning rather than regulating the development of skeletal structures. Developmental Dynamics 237:339,353, 2008. © 2008 Wiley-Liss, Inc. [source] Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal developmentDEVELOPMENTAL DYNAMICS, Issue 6 2007Mikala Egeblad Abstract Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone loss. Mmp2,/, mice have only mild aspects of these abnormalities, suggesting that MMP2 function is redundant during skeletal development in the mouse. Here, we report that Mmp2,/, mice with additional mutations that render type I collagen resistant to collagenase-mediated cleavage to TCA and TCB fragments (Col1a1r/r mice) have severe developmental defects resembling those observed in MMP2 -null humans. Composite Mmp2,/,;Col1a1r/r mice were born in expected Mendelian ratios but were half the size of wild-type, Mmp2,/,, and Col1a1r/r mice and failed to thrive. Furthermore, composite Mmp2,/,;Col1a1r/r animals had very abnormal craniofacial features with shorter snouts, bulging skulls, incompletely developed calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass was reduced concomitant with increased numbers of bone-resorbing osteoclasts and osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to degrade mutant collagen, offering a possible explanation for the genetic interaction between Mmp2 and Col1a1r. Thus, because mutations in the type I collagen gene alter the phenotype of mice with null mutations in Mmp2, we conclude that type I collagen is an important modifier gene for Mmp2. Developmental Dynamics 236:1683,1693, 2007. © 2007 Wiley-Liss, Inc. [source] Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth platesDEVELOPMENTAL DYNAMICS, Issue 1 2002Wen-Fang Wang Abstract Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4,5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates. © 2002 Wiley-Liss, Inc. [source] Vascular regression is required for mesenchymal condensation and chondrogenesis in the developing limbDEVELOPMENTAL DYNAMICS, Issue 3 2001Melinda Yin Abstract Vascular regression occurs during limb mesenchymal cell condensation and chondrogenesis, but it is unclear whether it is required for these processes or is a secondary phenomenon without major regulatory roles. To address this issue, beads presoaked with the potent angiogenic factor vascular endothelial growth factor (VEGF) were implanted in the vicinity of the prospective digit 2 in early chick embryo wing buds and the effects on angiogenesis and digit development were determined over time. We found that VEGF treatment caused a marked local increase in blood vessel number and density. Strikingly, this was accompanied by inhibition of digit 2 development as revealed by lack of expression of chondrogenic transcription factor Sox9 and absence of Alcian blue staining. Vascular distribution and skeletal development in adjacent areas remained largely unaffected. Inhibition of digit formation and excess vascularization were both reversible upon further embryonic growth and dissipation of VEGF activity. When supernumerary digits were induced at the anterior limb margin by retinoic acid treatment, their development was also preceded by vascular regression; interestingly, cotreatment with VEGF inhibited supernumerary digit development as well. Direct exposure of limb mesenchymal cells in micromass cultures to VEGF caused no obvious effects on condensation and chondrogenesis, indicating that VEGF effects are not due to direct action on skeletal cells. Our results are the first to provide evidence that vascular regression is required for mesenchymal condensation and chondrogenesis. A model of how patterning mechanisms and vascular regression may intersect and orchestrate limb skeletogenesis is proposed. © 2001 Wiley-Liss, Inc. [source] Chondrocranium and skeletal development of Phrynops hilarii (Pleurodira: Chelidae)ACTA ZOOLOGICA, Issue 4 2009Paula Bona Abstract The present study represents the first comprehensive contribution to the knowledge of the skeletal development of a pleurodiran turtle, Phrynops hilarii (Pleurodira, Chelidae). The most remarkable features found are: (1) absence of ascending process on pterygoquadrate cartilage; (2) presence of ossification centres for the epiotics; (3) as in other pleurodirans, dorsal ribs IX and X are ,sacralized'; (4) contact between ilium and carapace occurs later in ontogenetic development; (5) suture between ischia, pubes and plastron occurs in posthatching specimens; (6) contrary to previous interpretations, the phalangeal formula of the pes of P. hilarii is 2 : 3 : 3 : 3 : 5; (7) the hooked bone represents the fifth metatarsal. [source] Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1,HUMAN MUTATION, Issue 3 2009Frederick S. Kaplan Abstract Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant human disorder of bone formation that causes developmental skeletal defects and extensive debilitating bone formation within soft connective tissues (heterotopic ossification) during childhood. All patients with classic clinical features of FOP (great toe malformations and progressive heterotopic ossification) have previously been found to carry the same heterozygous mutation (c.617G>A; p.R206H) in the glycine and serine residue (GS) activation domain of activin A type I receptor/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor. Among patients with FOP-like heterotopic ossification and/or toe malformations, we identified patients with clinical features unusual for FOP. These atypical FOP patients form two classes: FOP-plus (classic defining features of FOP plus one or more atypical features) and FOP variants (major variations in one or both of the two classic defining features of FOP). All patients examined have heterozygous ACVR1 missense mutations in conserved amino acids. While the recurrent c.617G>A; p.R206H mutation was found in all cases of classic FOP and most cases of FOP-plus, novel ACVR1 mutations occur in the FOP variants and two cases of FOP-plus. Protein structure homology modeling predicts that each of the amino acid substitutions activates the ACVR1 protein to enhance receptor signaling. We observed genotype-phenotype correlation between some ACVR1 mutations and the age of onset of heterotopic ossification or on embryonic skeletal development. Hum Mutat 0, 1,12, 2008. © 2008 Wiley-Liss, Inc. [source] Insulin-like growth factor I in growing thoroughbredsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2007W. B. Staniar Summary The objective of this longitudinal study was to characterize growth and plasma insulin-like growth factor I (IGF-I) concentrations in pasture-raised thoroughbreds fed two sources of dietary energy. Mares and foals were randomly assigned to either a sugar and starch (SS) or fat and fibre (FF)-rich feed, and plasma IGF-I and growth were measured once a month from 1 to 16 months of age. These dependent variables were also compared with day length and ambient temperature. There was an association between plasma IGF-I concentration and average daily gain (ADG) (r = 0.32, p < 0.001). There were also clear seasonal patterns in both ADG and plasma IGF-I, with high values in June and May, and a low value in March. Plasma IGF-I and ADG were positively associated with day length and temperature. Plasma IGF-I was never higher (p > 0.10) in the FF group when compared with the SS group, and was higher in the SS group during a rapid growth phase in the spring of year 2 (p < 0.10). The results establish an association between ADG and IGF-I in the horse and indicate that environment and age may influence this relationship. In addition, plasma IGF-I is influenced by dietary energy source at particular times of year. This link has important implications in designing feeding management strategies that are aimed at addressing skeletal development. [source] Charles Darwin, embryology, evolution and skeletal plasticityJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2010B. K. Hall Summary Darwin provided us with the theory of evolutionary change through natural selection. Just as important to the science of biology was Darwin's recognition that all organisms could be classified and were related to one another because they arose from a single common universal ancestor , what we know as the universal tree of life (UtoL). All the features of the skeletal biology of fish therefore can be explained, both in an evolutionary framework (ultimate causation) and in the framework of development, growth and physiology (proximate causation). Neither approach is complete without the other. I will outline the elements of Darwin's theories on evolution and classification and, as importantly, discuss what was missing from Darwin's theories. An important class of evidence for evolution used by Darwin came from embryology, both comparative embryology and the existence of vestiges and atavisms. After discussing this evidence I examine some fundamental features of skeletal development and evolution These include: the presence of four skeletal systems in all vertebrates; the existence of two skeletons, one based on cartilage, the other on bone and dentine; the modular nature of skeletal development and evolution; and the plasticity of the skeleton in response to either genetic or environmental changes. [source] Habitual Levels of Physical Activity Influence Bone Mass in 11-Year-Old Children From the United Kingdom: Findings From a Large Population-Based Cohort,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Jon H Tobias MD Abstract We examined the influence of habitual levels of physical activity on bone mass in childhood by studying the relationship between accelerometer recordings and DXA parameters in 4457 11-year-old children. Physical activity was positively related to both BMD and bone size in fully adjusted models. However, further exploration revealed that this effect on bone size was modified by fat mass. Introduction: Exercise interventions have been reported to increase bone mass in children, but it is unclear whether levels of habitual physical activity also influence skeletal development. Materials and Methods: We used multivariable linear regression to analyze associations between amount of moderate and vigorous physical activity (MVPA), derived from accelerometer recordings for a minimum of 3 days, and parameters obtained from total body DXA scans in 4457 11-year-old boys and girls from the Avon Longitudinal Study of Parents and Children. The influence of different activity intensities was also studied by stratification based on lower and higher accelerometer cut-points for moderate (3600 counts/minute) and vigorous (6200 counts/minute) activity, respectively. Results: MVPA was positively associated with lower limb BMD and BMC adjusted for bone area (aBMC; p < 0.001, adjusted for age, sex, socio-economic factors, and height, with or without additional adjustment for lean and fat mass). MVPA was inversely related to lower limb bone area after adjusting for height and lean mass (p = 0.01), whereas a positive association was observed when fat mass was also adjusted for (p < 0.001). Lower limb BMC was positively related to MVPA after adjusting for height and lean and fat mass (p < 0.001), whereas little relationship was observed after adjusting for height and lean mass alone (p = 0.1). On multivariable regression analysis using the fully adjusted model, moderate activity exerted a stronger influence on lower limb BMC compared with light activity (light activity: 2.9 [1.2,4.7, p = 0.001]; moderate activity: 13.1 [10.6,15.5, p < 0.001]; regression coefficients with 95% confidence intervals and p values). Conclusions: Habitual levels of physical activity in 11-year-old children are related to bone size and BMD, with moderate activity exerting the strongest influence. The effect on bone size (as reflected by DXA-based measures of bone area) was modified by adjustment for fat mass, such that decreased fat mass, which is associated with higher levels of physical activity, acts to reduce bone size and thereby counteract the tendency for physical activity to increase bone mass. [source] Targeted Expression of SHH Affects Chondrocyte Differentiation, Growth Plate Organization, and Sox9 Expression,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2004Sara Tavella Abstract The role of Hedgehogs (Hh) in murine skeletal development was studied by overexpressing human Sonic Hedgehog (SHH) in chondrocytes of transgenic mice using the collagen II promoter/enhancer. Overexpression caused a lethal craniorachischisis with major alterations in long bones because of defects in chondrocyte differentiation. Introduction: Hedgehogs (Hhs) are a family of secreted polypeptides that play important roles in vertebrate development, controlling many critical steps of cell differentiation and patterning. Skeletal development is affected in many different ways by Hhs. Genetic defects and anomalies of Hhs signaling pathways cause severe abnormalities in the appendicular, axial, and cranial skeleton in man and other vertebrates. Materials and Methods: Genetic manipulation of mouse embryos was used to study in vivo the function of SHH in skeletal development. By DNA microinjection into pronuclei of fertilized oocytes, we have generated transgenic mice that express SHH specifically in chondrocytes using the cartilage-specific collagen II promoter/enhancer. Transgenic skeletal development was studied at different embryonic stages by histology. The expression pattern of specific chondrocyte molecules was studied by immunohistochemistry and in situ hybridization. Results: Transgenic mice died at birth with severe craniorachischisis and other skeletal defects in ribs, sternum, and long bones. Detailed analysis of long bones showed that chondrocyte differentiation was blocked at prehypertrophic stages, hindering endochondral ossification and trabecular bone formation, with specific defects in different limb segments. The growth plate was highly disorganized in the tibia and was completely absent in the femur and humerus, leading to skeletal elements entirely made of cartilage surrounded by a thin layer of bone. In this cartilage, chondrocytes maintained a columnar organization that was perpendicular to the bone longitudinal axis and directed toward its outer surface. The expression of SHH receptor, Patched-1 (Ptc1), was greatly increased in all cartilage, as well as the expression of parathyroid hormone-related protein (PTHrP) at the articular surface; while the expression of Indian Hedgehog (Ihh), another member of Hh family that controls the rate of chondrocyte maturation, was greatly reduced and restricted to the displaced chondrocyte columns. Transgenic mice also revealed the ability of SHH to upregulate the expression of Sox9, a major transcription factor implicated in chondrocyte-specific gene expression, in vivo and in vitro, acting through the proximal 6.8-kb-long Sox9 promoter. Conclusion: Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones. [source] RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory regionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Marcie Fowler Abstract The RUNX transcription factors (RUNX1, RUNX2, and RUNX3) play essential roles in hematopoiesis and skeletal development. Consistent with these roles in differentiation and cell cycle, the activity of both RUNX1 and RUNX3 is perturbed in cancer. To determine a role for the RUNX factors in prostate biology, we investigated the expression of RUNX factors in prostate epithelial cell lines and normal prostate tissue. RUNX1, RUNX2, and RUNX3 were expressed in both normal prostate tissue and an immortalized, non-transformed cell line. We found that prostate cancer-derived cell lines expressed RUNX1 and RUNX2, but not RUNX3. Next, we sought to identify prostate-specific genes whose expression could be regulated by RUNX proteins. Four consensus RUNX sites are located within the prostate-specific antigen (PSA) regulatory region. Chromatin immunoprecipitation (ChIP) analysis showed that RUNX1 is specifically bound to the PSA regulatory region in LNCaP cells. RUNX1 and RUNX2 activated the PSA regulatory region alone or cooperatively with prostate- derived ETS factor (PDEF) and RUNX1 physically associated with PDEF. Taken together, our results suggest that RUNX factors participate in prostate epithelial cell function and cooperate with an Ets transcription factor to regulate PSA gene expression. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2004Meenal Mehrotra Abstract Osteoblastic migration and proliferation in response to growth factors are essential for skeletal development, bone remodeling, and fracture repair, as well as pathologic processes, such as metastasis. We studied migration in response to platelet-derived growth factor (PDGF, 10 ng/ml) in a wounding model. PDGF stimulated a twofold increase in migration of osteoblastic MC3T3-E1 cells and murine calvarial osteoblasts over 24,48 h. PDGF also stimulated a tenfold increase in 3H-thymidine (3H-TdR) incorporation in MC3T3-E1 cells. Migration and DNA replication, as measured by BrdU incorporation, could be stimulated in the same cell. Blocking DNA replication with aphidicolin did not reduce the distance migrated. To examine the role of mitogen-activated protein (MAP) kinases in migration and proliferation, we used specific inhibitors of p38 MAP kinase, extracellular signal regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). For these signaling studies, proliferation was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) using flow cytometry. Inhibition of the p38 MAP kinase pathway by SB203580 and SB202190 blocked PDGF-stimulated migration but had no effect on proliferation. Inhibition of the ERK pathway by PD98059 and U0126 inhibited proliferation but did not inhibit migration. Inhibition of JNK activity by SP600125 inhibited both migration and proliferation. Hence, the stimulation of migration and proliferation by PDGF occurred by both overlapping and independent pathways. The JNK pathway was involved in both migration and proliferation, whereas the p38 pathway was predominantly involved in migration and the ERK pathway predominantly involved in proliferation. © 2004 Wiley-Liss, Inc. [source] Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactionsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007Anita Woods Chondrocyte differentiation is a multi-step process characterized by successive changes in cell morphology and gene expression. In addition to tight regulation by numerous soluble factors, these processes are controlled by adhesive events. During the early phase of the chondrocyte life cycle, cell,cell adhesion through molecules such as N-cadherin and neural cell adhesion molecule (N-CAM) is required for differentiation of mesenchymal precursor cells to chondrocytes. At later stages, for example in growth plate chondrocytes, adhesion signaling from extracellular matrix (ECM) proteins through integrins and other ECM receptors such as the discoidin domain receptor (DDR) 2 (a collagen receptor) and Annexin V is necessary for normal chondrocyte proliferation and hypertrophy. Cell,matrix interactions are also important for chondrogenesis, for example through the activity of CD44, a receptor for Hyaluronan and collagens. The roles of several signaling molecules involved in adhesive signaling, such as integrin-linked kinase (ILK) and Rho GTPases, during chondrocyte differentiation are beginning to be understood, and the actin cytoskeleton has been identified as a common target of these adhesive pathways. Complete elucidation of the pathways connecting adhesion receptors to downstream effectors and the mechanisms integrating adhesion signaling with growth factor- and hormone-induced pathways is required for a better understanding of physiological and pathological skeletal development. J. Cell. Physiol. 213: 1,8, 2007. © 2007 Wiley-Liss, Inc. [source] Epidermal growth factor stimulates proton efflux from chondrocytic cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002Kevin E.H. Lui Proton efflux from chondrocytes alters the extracellular pH and ionic composition of cartilage, and influences the synthesis and degradation of extracellular matrix. Epidermal growth factor (EGF) promotes chondrocyte proliferation during skeletal development and accumulates in the synovial fluid in rheumatoid arthritis. The purpose of this study was to investigate the effect of EGF on proton efflux from chondrocytes. When monitored using a Cytosensor microphysiometer, EGF was found to rapidly activate proton efflux from CFK2 chondrocytic cells and rat articular chondrocytes. The actions of EGF were concentration-dependent with half-maximal effects at 0.3,0.7 ng/ml. Partial desensitization and time-dependent recovery of the response were observed following repeated exposures to EGF. EGF-induced proton efflux was dependent on extracellular glucose, and inhibitors of Na+/H+ exchange (NHE) markedly attenuated the initial increase in proton efflux. The response was diminished by inhibitors of phosphatidylinositol 3-kinase and phospholipase C, but not by inhibitors of MEK (MAPK/ERK kinase) or protein kinase A or C. Thus, EGF-induced proton efflux involves glucose metabolism and NHE, and is regulated by a discrete subset of EGF-activated signaling pathways. In vivo, proton efflux induced by EGF may lead to an acidic environment, enhancing turnover of cartilage matrix during development and in rheumatoid arthritis. © 2002 Wiley-Liss, Inc. [source] Altered binding of MYF-5 to FOXE1 promoter in non-syndromic and CHARGE-associated cleft palateJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009Mario Venza Background:, Three different homozygous loss-of-function mutations of the Forkhead box E1 (FOXE1) gene have been associated with syndromic cleft palate. Here, we screened the entire promoter region to identify the variations in significant consensus motifs affecting FOXE1 transcription. Method:, Genomic DNAs of 35 cleft palate patients, 10 of whom with CHARGE association, 80 unrelated healthy people and 80 unaffected first-degree relatives were analysed by automatic sequencing. The Transcription Element Search System program was employed to identify transcription factor binding sites. The protein-DNA complexes were observed using DNA band-shift assays and oligonucleotide competition analyses. Real-time PCR was used to estimate FOXE1 expression at mRNA level. Results:, In 11 non-syndromic cleft palate patients, a novel non-coding polymorphism (C,G) in the 5,-untranslated region of FOXE1 was found. The variation fell into a putative consensus sequence for the transcription factor MYF-5 and completely impaired the ability of MYF -5 to bind to its motif, as shown by EMSA experiments. As a consequence, a significantly reduced FOXE1 mRNA expression was observed. Conclusions:, In 45% of non-syndromic cleft palate patients, a novel homozygous polymorphism that prevented the binding of MYF -5 to FOXE1 promoter and affected the FOXE1 expression was found. As recent data show the role of MYF-5 in the muscle-dependent craniofacial skeletal development and in the fusion of primary palate and secondary palate, the results reported here strongly suggest a more significant involvement of this factor in the cleft palate onset. [source] Modulation of Wnt signaling influences fracture repairJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010David E. Komatsu Abstract While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5,/,) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5,/, and Lrp5+/+ mice were untreated, while C57BL/6 mice were treated 2×/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5,/, mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD, and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:928,936, 2010 [source] Transforming growth factor-,1 induced alteration of skeletal morphogenesis in vivoJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2004Cristin M. Ferguson Abstract Transforming growth factor beta (TGF-,) is expressed in the growth plate and is an important regulator of chondrocyte maturation. Loss of function results in premature chondrocyte maturation both in vitro and in vivo. While TGF-, inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-, has not been well characterized in an in vivo development model. Addition of Affi-gel agarose beads loaded with TGF-,1 (10 ng/,l) to developing stage 24,25 chick limb buds resulted in limb shortening and altered morphology. In situ hybridization studies showed down regulation of Indian hedgehog (ihh), bone morphogenetic protein 6 (bmp6), and collagen type X (colX) expression, markers of chondrocyte maturation, in TGF-,1 treated limbs. TGF-,1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-, during skeletal development. A more complete understanding of the role of TGF-, and its down-stream signals will lead to improved understanding and treatment of cartilage diseases. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Ethanol Alters the Osteogenic Differentiation of Amniotic Fluid-Derived Stem CellsALCOHOLISM, Issue 10 2010Jennifer A. Hipp Background:, Fetal alcohol spectrum disorder (FASD) is a set of developmental defects caused by prenatal alcohol exposure. Clinical manifestations of FASD are highly variable and include mental retardation and developmental defects of the heart, kidney, muscle, skeleton, and craniofacial structures. Specific effects of ethanol on fetal cells include induction of apoptosis as well as inhibition of proliferation, differentiation, and migration. This complex set of responses suggests that a bioinformatics approach could clarify some of the pathways involved in these responses. Methods:, In this study, the responses of fetal stem cells derived from the amniotic fluid (AFSCs) to treatment with ethanol have been examined. Large-scale transcriptome analysis of ethanol-treated AFSCs indicates that genes involved in skeletal development and ossification are up-regulated in these cells. Therefore, the effect of ethanol on osteogenic differentiation of AFSCs was studied. Results:, Exposure to ethanol during the first 48 hours of an osteogenic differentiation protocol increased in vitro calcium deposition by AFSCs and increased alkaline phosphatase activity. In contrast, ethanol treatment later in the differentiation protocol (day 8) had no significant effect on the activity of alkaline phosphatase. Conclusions:, These results suggest that transient exposure of AFSCs to ethanol during early differentiation enhances osteogenic differentiation of the cells. [source] Skeletal and Pigmentation Defects following Retinoic Acid Exposure in Larval Summer Flounder, Paralichthys dentatusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2007Gabriela M. Martinez Supplementation of larval diets with vitamin A (VA) is routinely and successfully used to stimulate pigmentation development in hatchery-reared flatfishes. However, excess dietary VA can lead to high levels of its metabolite retinoic acid (RA) and has been associated with the occurrence of skeletal deformities, presumably via RA toxicity. We reared summer flounder larvae, Paralichthys dentatus, in water containing 0- to 20-nM RA to assess its effects on postmetamorphic pigmentation and on skeletal development. RA exposure disrupted pigmentation development: treated tanks had a smaller percentage of normally pigmented fish than did controls, with increased numbers of both hypo- and hyperpigmented individuals. Exposure also affected the development of several skeletal features: RA treatment correlated with a significant increase in the severity of defects in jaws, fins, hypurals, and vertebrae compared with control groups. [source] A comparative study of growth, skeletal development and eggshell composition in some species of birdsJOURNAL OF ZOOLOGY, Issue 4 2004Jonas Blom Abstract Some studies of birds suggest that the development of the skeleton may invoke a constraint on the rate of postnatal growth. Other studies have shown that the eggshell is the major source of calcium for skeletal development of the embryo. To test whether avian growth rate is indeed associated with different patterns of skeletal development, we compared the degree of skeletal ossification of the long bones of the wing and the leg of one slowly growing precocial species (quail Coturnix japonica) with that of two rapidly growing altricial species (starling Sturnus vulgaris and fieldfare Turdus pilaris). The degree of skeletal ossification of the long bones of the wings and legs of lines of quails that had undergone long-term selection for high- and low-growth rate, respectively, also was compared with a non-selected control line. Next, the fine structure of the inner eggshell surface (mammillary layer) of both pre- and post-incubated eggs, i.e. before and after embryonic development/calcium removal was compared. The data show that the skeleton of the more rapidly growing species and lines was less ossified than that of the more slowly growing ones. This difference appeared to be associated with different rates of calcium removal from the eggshell. Removal was more extensive in eggs of quail than in eggs of starling and fieldfare, i.e. more extensive in shells with a high number of mammillary tips per unit of surface area than in shells with a lower number. It is therefore concluded that growth rate is of fundamental importance for the pattern of skeletal development. Moreover, the mammillary density varies between different bird species, it is suggested, in order to support the different rates of calcium removal by developing embryos. [source] Calcium and Exercise Affect the Growing SkeletonNUTRITION REVIEWS, Issue 11 2005Jo M. Welch PhD Adequate dietary calcium and bone-stimulating exercise during growth are known to affect skeletal development, but the combined effects of dietary calcium and osteogenic exercise have received scant attention. Animal research has showed a compensatory effect of impact loading on calcium-deprived bones, while various human studies have suggested compensatory, additive, or possibly synergistic effects in certain skeletal locations. Current evidence suggests that the best strategy for strong bones by the end of childhood may be either high-impact exercise with a moderate or greater calcium intake or a combination of moderate-impact exercise and adequate calcium during growth. [source] Quantifying calcium intake in school age children: Development and validation of the Calcium Counts!© food frequency questionnaire,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2010Babette S. Zemel Quantifying dietary behavior is difficult and can be intrusive. Calcium, an essential mineral for skeletal development during childhood, is difficult to assess. Few studies have examined the use of food frequency questionnaires (FFQs) for assessing calcium intake in school-age children. This study evaluated the validity and reliability of the Calcium Counts!© FFQ (CCFFQ) for estimating calcium intake in school children in the US. Healthy children, aged 7,10 years (n = 139) completed the CCFFQ and 7-day weighed food records. A subset of subjects completed a second CCFFQ within 3.6 months. Concurrent validity was determined using Pearson correlations between the CCFFQ and food record estimates of calcium intake, and the relationship between quintiles for the two measures. Predictive validity was determined using generalized linear regression models to explore the effects of age, race, and gender. Inter- and intra-individual variability in calcium intake was high (>300 mg/day). Calcium intake was ,300 mg/day higher by CCFFQ compared to food records. Concurrent validity was moderate (r = 0.61) for the entire cohort and higher for selected subgroups. Predictive validity estimates yielded significant relationships between CCFFQ and food record estimates of calcium intake alone and in the presence of such potential effect modifiers as age group, race, and gender. Test,retest reliability was high (r = 0.74). Although calcium intake estimated by the CCFFQ was greater than that measured by food records, the CCFFQ provides valid and reliable estimates of calcium intake in children. The CCFFQ is especially well-suited as a tool to identify children with low calcium intakes. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] Markers of physiological stress in juvenile bonobos (Pan paniscus): Are enamel hypoplasia, skeletal development and tooth size interrelated?AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009John R. Lukacs Abstract A reduction in enamel thickness due to disrupted amelogenesis is referred to as enamel hypoplasia (EH). Linear EH in permanent teeth is a widely accepted marker of systemic physiological stress. An enigmatic, nonlinear form of EH commonly manifest in great ape and human deciduous canines (dc) is known as localized hypoplasia of primary canines (LHPC). The etiology of LHPC and what it signifies,localized traumatic or systemic physiological stress,remains unclear. This report presents frequency data on LHPC, hypostotic cranial traits, and tooth size in a sample of juvenile bonobos, then tests hypotheses of intertrait association that improve knowledge of the etiology and meaning of LHPC. The fenestration hypothesis is tested using hypostotic cranial traits as a proxy for membrane bone ossification, and the relationship between tooth size, LHPC, and hypostosis is investigated. Macroscopic observations of EH, hypostotic traits, and measurements of buccolingual tooth size were conducted according to established standards. LHPC was found in 51.2% of bonobos (n = 86) and in 26% of dc teeth (n = 269). Hypostotic traits were observed in 55.2% of bonobos (n = 96). A test of the association between LHPC and hypostosis yielded nonsignificant results (,2 = 2.935; P = 0.0867). Primary canines were larger in specimens with LHPC than in unaffected specimens (paired samples t test; udc, P = 0.011; ldc, P = 0.018), a result consistent with the fenestration hypothesis of LHPC pathogenesis. Hypostosis was not associated with differences in tooth size (P > 0.05). LHPC may be an indirect indicator of physiological stress, resulting from large, buccally displaced primary canines. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] Asymmetry of the os pubis: Implications for the Suchey-Brooks methodAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009Rebecca S. Overbury Abstract Studies of skeletal development frequently document populational incidences of bilateral asymmetry. Degenerative morphological skeletal changes, attributed to age related and irregular ossification, may also progress asymmetrically, either as the result of asymmetric biomechanical factors expressed over the lifespan, asymmetric expression of physiological processes, or progressive magnification of asymmetry acquired previously during development. This study illustrates the effects of bilateral asymmetry on age at death estimates obtained from human skeletal remains. The Suchey-Brooks method, which uses the pubic symphyseal face for age estimation (Katz and Suchey, Am J Phys Anthropol 69 1986 427,435), was selected for the study based on its widespread use. Asymmetry in the Suchey-Brooks symphyseal age phases was found in over 60% of a sample composed of 20th century White male individuals from 18 to 86 years of age (N = 130). However, results suggest that the presence of asymmetry does not compromise the accuracy of the Suchey-Brooks method if the morphologically older symphyseal face of an asymmetric individual is used to estimate age at death. In addition, weak directional asymmetry and a correlation between age and asymmetry were found. This suggests that a comparison of asymmetry in this area with that in other skeletal areas, where the factors originating and influencing asymmetry are better understood, may be useful in better understanding the biological processes which underlie the age markers used in the Suchey-Brooks method. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||