Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bone Development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2002

The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis.

The Wnt antagonist Frzb-1 is expressed during limb skeletogenesis, but its roles in this complex multistep process are not fully understood. To address this issue, we determined Frzb-1 gene expression patterns during chick long bone development and carried out gain- and loss-of-function studies by misexpression of Frzb-1, Wnt-8 (a known Frzb-1 target), or different forms of the intracellular Wnt mediator LEF-1 in developing limbs and cultured chondrocytes. Frzb-1 expression was quite strong in mesenchymal prechondrogenic condensations and then characterized epiphyseal articular chondrocytes and prehypertrophic chondrocytes in growth plates. Virally driven Frzb-1 misexpression caused shortening of skeletal elements, joint fusion, and delayed chondrocyte maturation, with consequent inhibition of matrix mineralization, metalloprotease expression, and marrow/bone formation. In good agreement, misexpression of Frzb-1 or a dominant-negative form of LEF-1 in cultured chondrocytes maintained the cells at an immature stage. Instead, misexpression of Wnt-8 or a constitutively active LEF-1 strongly promoted chondrocyte maturation, hypertrophy, and calcification. Immunostaining revealed that the distribution of endogenous Wnt mediator beta-catenin changes dramatically in vivo and in vitro, from largely cytoplasmic in immature proliferating and prehypertrophic chondrocytes to nuclear in hypertrophic mineralizing chondrocytes. Misexpression of Frzb-1 prevented beta-catenin nuclear relocalization in chondrocytes in vivo or in vitro. The data demonstrate that Frzb-1 exerts a strong influence on limb skeletogenesis and is a powerful and direct modulator of chondrocyte maturation, phenotype, and function. Phases of skeletogenesis, such as terminal chondrocyte maturation and joint formation, appear to be particularly dependent on Wnt signaling and thus very sensitive to Frzb-1 antagonistic action.

Animals↗
PubMed2003

Endothelin 1-mediated regulation of pharyngeal bone development in zebrafish.

Endothelin 1 (Edn1), a secreted peptide expressed ventrally in the primordia of the zebrafish pharyngeal arches, is required for correct patterning of pharyngeal cartilage development. We have studied mutants and morpholino-injected larvae to examine the role of the Edn1 signal in patterning anterior pharyngeal arch bone development during the first week after fertilization. We observe a remarkable variety of phenotypic changes in dermal bones of the anterior arches after Edn1 reduction, including loss, size reduction and expansion, fusion and shape change. Notably, the changes that occur appear to relate to the level of residual Edn1. Mandibular arch dermal bone fusions occur with severe Edn1 loss. In the dorsal hyoid arch, the dermal opercle bone is usually absent when Edn1 is severely reduced and is usually enlarged when Edn1 is only mildly reduced, suggesting that the same signal can act both positively and negatively in controlling development of a single bone. Position also appears to influence the changes: a branchiostegal ray, a dermal hyoid bone normally ventral to the opercle, can be missing in the same arch where the opercle is enlarged. We propose that Edn1 acts as a morphogen; different levels pattern specific positions, shapes and sizes of bones along the dorso-ventral axis. Changes involving Edn1 may have occurred during actinopterygian evolution to produce the efficient gill-pumping opercular apparatus of teleosts.

Animals↗
PubMedDate not supplied

Endochondral and intramembranous fetal bone development: osteoblastic cell proliferation, and expression of alkaline phosphatase, m-twist, and histone H4.

We have previously studied the expression of alkaline phosphatase (ALP) and alpha2(I) collagen (two phenotypic markers of osteoblastic cell differentiation) during development of the rat mandible, and the spatial and temporal distribution of the respective transcripts. Our current studies utilize the rat mandible and hind foot as in vivo model systems to investigate the relationship between osteoblastic differentiation and proliferation during intramembranous and endochondral bone formation. Pregnant rats, at 15.17, and 19 days of gestation were intraperitoneally injected with various doses of [3H]-thymidine, and sacrificed at various time intervals in order to label dividing embryonic osteoblastic and preosteoblastic cells. Cross sections through the mid-body of 15-day embryos showed [3H-thymidine dose-dependent labeling of a relatively high percentage of cells in the liver (49 +/- 8% at 440 muCi) and a lower percentage of cells of the developing vertebral cartilage (29 +/- 6% at 440 muCi). ALP-positive condensed mesenchyme--consisting of mandibular preosteoblast (15 days of gestation) showed a relatively high (32 +/- 5%) level of [3H]-thymidine labeling, compared to surrounding ALP-negative loose mesenchymal cells (22 +/- 1%). Similar results were observed in the developing hind foot of 19-day embryos for ALP-positive cells (15 +/- 6%) and surrounding ALP-negative cells (13 +/- 5%). In both the hind foot and the mandible an overall decrease in labeling was observed during bone development. RNA samples from these tissues show increasing amounts of ALP mRNA, and decreasing amounts of histone H4 mRNA between days 15 and 19 of gestation. These data indicate that a general inverse correlation between osteoblastic differentiation and proliferation, similar to the correlation previously described in cultured osteogenic cells, is also present in developing bones in vivo. However, these results indicate that ALP-positive preosteoblasts, committed to the osteoblastic lineage, maintain their proliferative capacity. In an attempt to elucidate underlying molecular mechanisms, we further investigated the levels of expression of m-twist in these tissues. This member of the basic helix-loop-helix family of transcription regulators has been previously implied as playing a role in osteoblast differentiation in culture. Our results demonstrate a decrease in m-twist levels during bone development in both the mandible and the hind foot.

Alkaline Phosphatase↗
PubMed2002

Effects of transforming growth factor-beta deficiency on bone development: a Fourier transform-infrared imaging analysis.

Transforming growth factor-beta 1 (TGF-beta1) is a cytokine member of the TGF-beta superfamily involved in the control of proliferation and differentiation of various cell types. TGF-beta1 plays an important role in bone formation and resorption. To determine the effect of TGF-beta1 deficiency on bone mineral and matrix, tibias from mice in which TGF-beta1 expression had been ablated (TGF-beta1 null) were analyzed and compared with background- and age-matched wild-type (WT) control animals by Fourier transform-infrared imaging (FTIRI) and histochemistry. FTIRI allows the characterization of nondemineralized thin tissue sections at the ultrastructural level with a spatial resolution of approximately 7 microm. The spectroscopic parameters calculated were: mineral-to-matrix ratio (previously shown to correspond to ash weight); mineral crystallinity (related to the crystallographically determined crystallite size and perfection in the apatite c-axis direction); and collagen maturity (related to the ratio of pyridinoline:deH-DHLNL collagen cross-links). Several fields were selected to represent different stages of bone development within the same specimen from the secondary ossification center to the distal diaphysis. Anatomically equivalent areas were compared as a function of age and genotype. The spectroscopic results were expressed both as color-coded images and as pixel population distributions for each of the three parameters monitored. Based on comparisons of histochemistry and FTIRI, there were distinctive age and genotype variations. At all ages examined, in the TGF-beta1 null mice growth plates, alkaline phosphatase (ALP) activity and collagen maturity were reduced, but no effect on mineral content or crystallinity was noted. In the TGF-beta1 null mice metaphyses, there was a persistence of trabeculae, but no significant alterations in mineral content or crystallinity. In contrast, mineral content, mineral crystallinity, and collagen maturity were reduced in the secondary ossification center and cortical bone of the TGF-beta1 null mice. These results, consistent with a mechanism of impaired bone maturation in the TGF-beta1 null mice, may be directly related to TGF-beta1 deficiency and indirectly to increased expression of inflammatory cytokines in the TGFbeta1 null mice.

Animals↗
PubMed1986

A longitudinal study of carpal bone development in Perthes' disease: its significance for both radiologic standstill and bilateral disease.

This paper reports a longitudinal study of carpal bone development in 125 children (98 boys, 27 girls) attending a clinic for Perthes' disease. The age at appearance of ossification in each carpal bone was estimated by studying consecutive radiographs obtained at six-months intervals. The results were compared with the findings for normal children published by Stuart et al. Three radiologic groups of carpal bone maturation are defined: not delayed (capitate and hamate); markedly delayed (triquetral and lunate); and slightly delayed (scaphoid, trapezium, and trapezoid). Overall, the bone age delay is severely abnormal at three to five years of chronologic age and indicates the time in development when general abnormalities occur. The mean age at diagnosis (and standard deviation) for 34 boys with skeletal standstill was 4.49 +/- 1.07 years, compared with 7.28 +/- 2.40 years for 51 boys without such standstill; the mean age at appearance of carpal bones was not significantly different between these two groups, suggesting an equally profound delay of carpal maturation in the group of later-diagnosed boys. Boys with bilateral hip disease show a significant delay in age at ossification of the trapezoid compared with boys who have unilateral disease. The immaturity of bone age may be present during a latent period and be of etiologic significance in the onset of the hip disease, but at present the evidence links it only with bilateral disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpal Bones↗
PubMed1995

Detection of transcripts and binding sites for colony-stimulating factor-1 during bone development.

Colony-stimulating factor-1 (CSF-1), originally characterized as the growth factor for the cells of the mononuclear phagocytic system, has been shown to be essential for osteoclast formation. The aim of the present study was twofold: (i) to investigate the expression of transcripts encoding CSF-1; and (ii) to detect binding sites for CSF-1 during bone development. As a model, metatarsal rudiments from embryonic mice of different ages were used, an in vivo system allowing one to follow osteoclast formation. In 16-day-old embryos, proliferating osteoclast precursors are located on the outer surface of the rudiments. They differentiate subsequently to post-mitotic precursors. At 18 days, the precursors fuse and the mature osteoclasts invade the mineralized cartilage of the rudiments to excavate the future bone marrow cavity. Within this study, in situ hybridization on sections of whole paws from 17-day-old embryos revealed CSF-1 transcripts to be present in cells lining the outside of the midregion of the metatarsals. One day later, cells containing CSF-1 mRNA were found within the mineralized cartilage. The levels of transcripts encoding CSF-1 were further increased in the bone rudiments of newborn animals. Binding sites for CSF-1 on cells in close proximity of the metatarsals were detected at embryonic age 17 days, but not before. At this stage, cells binding CSF-1 were located on the periosteum of the midregion of the metatarsal rudiment. At 18 days, cells expressing high levels of CSF-1 binding sites had invaded the mineralized cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets.

This perspective paper presents a hypothesis that links abnormalities of bone material with densitometric findings in two congenital metabolic bone disorders, osteogenesis imperfecta type I (OI) and X-linked hypophosphatemic rickets (XLH). Analyses of iliac bone samples from OI patients have shown that material bone density is elevated and that the bone material is abnormally stiff in this disorder. Therefore, a given mechanical load on an OI bone will generate a smaller than normal deformation. This in turn should lead osteocytes, the putative mechanosensing cells, to systematically underestimate the prevailing mechanical forces. According to the mechanostat model, bone strength should then be adapted to the underestimated mechanical loads, which means that bone architecture and mass remain below requirements. Available densitometric studies are in accordance with this hypothesis. In XLH, a mild mineralization defect persists despite treatment. This mineralization defect should lead to soft bone material. In analogy to the above model for OI, mechanical loads should be overestimated, resulting in increased densitometric parameters of bone strength. Indeed, lumbar spine areal bone mineral density is usually elevated in such patients.

Biomechanical Phenomena↗
PubMed2001

Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development.

Vertebrate skeletogenesis requires a well-coordinated transition from chondrogenesis to osteogenesis. Hypertrophic chondrocytes in the growth plate play a pivotal role in this transition. Parathyroid hormone-related peptide (PTHrP), synthesized in the periarticular growth plate, regulates the site at which hypertrophy occurs. By comparing PTH/PTHrP receptor(-/-)/wild-type (PPR(-/-)/wild-type) chimeric mice with IHH(-/-);PPR(-/-)/wild-type chimeric and IHH(-/-)/wild-type chimeric mice, we provide in vivo evidence that Indian hedgehog (IHH), synthesized by prehypertrophic and hypertrophic chondrocytes, regulates the site of hypertrophic differentiation by signaling to the periarticular growth plate and also determines the site of bone collar formation in the adjacent perichondrium. By providing crucial local signals from prehypertrophic and hypertrophic chondrocytes to both chondrocytes and preosteoblasts, IHH couples chondrogenesis to osteogenesis in endochondral bone development.

Animals↗
PubMed1993

Restricted expression of Mov13 mutant alpha 1(I) collagen gene in osteoblasts and its consequences for bone development.

Cell type-specific differences in the transcriptional control of the mouse gene coding for the alpha 1 chain of collagen type I (Col1a1) have been revealed previously with the help of the Mov13 mouse strain which carries a retroviral insert in the first intron of the gene. Transcription of this mutant Col1a1 allele is completely blocked in all mesodermal cell types tested so far, with the exception of the odontoblast where it is expressed at an apparently normal rate (Kratochwil et al. [1989] Cell 57:807-816). To define the tissue specificity of the mutant allele more precisely, we have now studied its expression in osteoblasts, another skeletogenic cell type which, like odontoblasts, produces high amounts of collagen I. Evidence for transcription of the Mov13 allele was obtained by in situ hybridization in homozygous (M/M) and heterozygous (M/+) bone tissue, in grafts as well as in vivo. The presence of mouse collagen I and the development of bone tissue were demonstrated in M/M skeletal elements grown on the chick chorioallantoic membrane (CAM). Further support for expression of the mutant gene was obtained from two 16 day M/M fetuses in vivo. Bone tissue of diverse embryological origin (vertebrae and ribs of somitic origin, long bones derived from lateral plate, calvariae from head paraxial mesoderm, and mandibulae from head neural crest) expresses the mutant allele. However, in situ hybridization experiments indicate that only a subpopulation of osteoblasts is capable of transcribing it at a high rate, resulting in severe impairment of bone development in grafts and in vivo. Therefore, osteoblasts, in comparison to odontoblasts and fibroblast-like cells, assume an intermediate position with respect to transcription of the Mov13 allele. We suggest that this diversity in the utilization of the mutant collagen gene reflects cell type-specific differences in the transcriptional regulation of the wild type (wt) Col1a1 gene.

Alleles↗
PubMed1995

Expression of prostaglandin E receptor subtypes in bone: expression of EP2 in bone development.

Prostaglandin (PG) E2 displays physiological and pharmacological action in various tissues including bone. It increases intracellular Ca, and stimulates or inhibits cAMP production through the PGE receptor subtypes EP1, EP2, and EP3, respectively. These receptor subtypes have been recently cloned. In the present study, we investigate the expression of these receptor subtypes in bone tissue. RT-PCR revealed that EP1, EP2, and EP3 were expressed in rat calvariae and that osteoblastic cells (MC3T3-E1) expressed EP1 and EP2. In situ hybridization analysis using cryosection of neonatal calvariae revealed that EP2 was expressed by osteoblasts and cells not in contact with bone, probably including preosteoblasts. EP2 expression was observed at an early stage in calvarial development, at 14 days prenatal. EP2 expression was also observed at day 3 in rat bone marrow cell culture in which bone-like mineralized nodules are formed at day 8. It has been established that PGE2 response accompanying cAMP production is one of the characteristics of osteoblasts. The present results indicate that this phenotype appears at an early stage of osteoblastic differentiation and bone development.

3T3 Cells↗