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At least 145 records · Page 8Linked to original sources
PubMed2003

Performance and bone development in broiler chickens given 25-hydroxycholecalciferol.

1. A series of 5 trials was conducted with Cobb chickens in order to determine the effect of 25-hydroxycholecalciferol (25OHD3) on their performance and bone development under adequate Calcium (Ca) and Phosphorus (P) supplementation, and under moderate dietary restriction of Ca and P. Formulated beadlets of 25OHD3, trade name HY-D (IsoGen, Naperville, IL, USA) were used as the 25OHD3 source. 2. Five to 10 microg of cholecalciferol (vitamin D3) or 25OHD3/kg diet were sufficient to ensure normal body weight (BW) and bone ash in chickens under continuous lighting. The two materials had similar effects on BW and bone ash. 3. In one out of the three experiments, 25OHD3 increased BW and BW gain, while in the others it had a similar effect to that of vitamin D3, or even a slight negative effect in a trial conducted on the floor, in which the diets were supplemented with the D sources at 75 microg/kg. The effects of both D sources on bone ash and on the severity or frequency of tibial dischondroplasia were similar. 4. 25OHD3 restrained the effect of moderate dietary P restriction, but not of Ca restriction, on BW gain and bone ash in 22-d-old chickens. This effect could not be explained by an higher P bioavailability in the 25OHD3-fed chickens.

Animal Feed↗
PubMed2006

Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development.

Wdr5 accelerates osteoblast and chondrocyte differentiation in vitro, and is developmentally expressed in osteoblasts as well as in proliferating and hypertrophic chondrocytes. To investigate the role of Wdr5 during endochondral bone development, transgenic mice overexpressing Wdr5 under the control of the 2.3-kb fragment of the mouse alpha(1) I collagen promoter were generated. The transgene was specifically expressed in the osteoblasts of transgene positive mice and was absent in the growth plate. Histological analyses at embryonic day 14.5 demonstrated that the humeri of transgene positive embryos were longer than those isolated from wild-type littermates largely due to an expansion of the hypertrophic chondrocyte layer. Acceleration of osteoblast differentiation was observed with greater and more extensive expression of type I collagen and more extensive mineral deposition in the bone collar of transgene positive embryos. Acceleration of vascular invasion was also observed in transgene positive mice. Postnatal analyses of transgenic mice confirmed persistent acceleration of osteoblast differentiation. Targeted expression of Wdr5 to osteoblasts resulted in earlier activation of the canonical Wnt signaling pathway in the bone collar as well as in primary calvarial osteoblast cultures. In addition, overexpression of Wdr5 increased the expression of OPG, a target of the canonical Wnt signaling pathway. Overall, our findings suggest that Wdr5 accelerates osteoblast differentiation in association with activation of the canonical Wnt pathway.

Animals↗
PubMed1997

[Differences in temporal bone development in various ear diseases].

To investigate the differences in temporal bone development in various ear diseases--bilateral Meniere's disease (n = 13), unilateral Meniere's disease (n = 41), unilateral chronic otitis media (COM) (n = 25), temporal bone fracture (n = 9) and otosclerosis (n = 12)--the following 4 distances on a temporal bone CT slice encompassing the lateral semicircular canal (LSC) were measured by using the NIH Image program. These distances included the minimal distance between the posterior semicircular canal (PSC) and the posterior petrous surface (PPS) (P-P distance), the minimal distance between the PSC and the LSC (P-L distance), the minimal distance between the vestibule and the PPS (V-P distance) and the minimal distance between the PSC and the anterior margin of the sigmoid sinus (P-S distance). Both the P-P and V-P distances showed significant differences among the ear diseases, but the P-L and P-S distance did not. Meniere's disease showed significantly shorter P-P and V-P distance especially in bilateral Meniere's disease than those in COM and otosclerosis (p < 0.05). Affected ears in unilateral Meniere's disease showed a shorter P-P distance than non-affected ears (p < 0.01). In contrast, both ears with otosclerosis showed significantly longer P-P and V-P distances than those in Meniere's disease, COM (p < 0.01) and temporal bone fracture (p < 0.05). COM and temporal bone fracture showed intermediate P-P and V-P distances, without a difference between the affected and non-affected ears. In conclusion, the development of the posterior part of the temporal bone is reduced in Meniere's disease and greatly increased in otosclerosis. These findings by CT may be useful for diagnosing ear diseases.

Ear Diseases↗
PubMed1997

Temporal changes of mRNA expression of matrix proteins and parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor in bone development.

Expression of parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor is one of the osteoblastic phenotypes; however, it has not been clear whether this phenotype expression is a marker of immature or mature osteoblasts. We examined the temporal expression pattern of PTH/PTHrP receptor in bone development in vivo and in vitro compared with the expression of other osteoblastic phenotypes: osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), alkaline phosphatase (ALP), and mineralization. Total RNA was extracted from rat calvariae, and cell culture of rat bone marrow at different developmental stages and then Northern blot hybridization were performed. Mineralization was detected with contact microradiography (CMR) in calvaria or with Alizarin Red S staining in bone marrow cell culture. Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation. Notably, PTH/PTHrP receptor was expressed at an early developmental stage (prenatal day 14 in calvaria, day 5 in culture) when mineralized tissue was not formed and other osteoblastic phenotypes were scarcely detected. Further study in cell culture revealed that the fold increase in cyclic adenosine monophosphate (cAMP) in response to PTH was elevated with the advance in the culture stage. These results indicate that mRNA expression of PTH/PTHrP receptor could be the early differentiation marker in osteoblastic lineage and that the levels of cAMP production in response to PTH represent the stage of osteoblastic differentiation.

Alkaline Phosphatase↗
PubMed1987

Earliest evidence of cartilage and bone development in embryonic life.

Some aspects of the development of cartilage and bone during embryonic life are discussed in this review and an attempt is made to show that studies of development, even when performed on species far removed from humans, are relevant to clinical orthopedic surgery. Initially, some definitions of skeletal tissues and cells are presented to illustrate the nontrivial problem of how to tell whether cells are capable of becoming osteoblasts or chondroblasts and of depositing bone or cartilage. This leads to a discussion of the best criteria to use to identify differentiating osteogenic and chondrogenic cells. Cytodifferentiation is immediately preceded by the appearance of the membranous skeleton, consisting of the mesenchymal condensations in which bone and cartilage will develop. Condensation formation in normal development and defective condensations leading to abnormal skeletogenesis are related to cellular properties of mesenchymal cells. The remainder of the review is on the development of membrane bone in the craniofacial skeleton, subperiosteal bone in embryonic avian long bones, and subperiosteal and endochondral bone in developing mammalian long bones. In each case the emphasis is on the embryologic origins of the skeletogenic cells, cell migration, and the factors and influences involved in the initiation of cell differentiation. The relevance of developing systems to clinical practice is stressed throughout.

Animals↗
PubMed2004

Altered endochondral bone development in matrix metalloproteinase 13-deficient mice.

The assembly and degradation of extracellular matrix (ECM) molecules are crucial processes during bone development. In this study, we show that ECM remodeling is a critical rate-limiting step in endochondral bone formation. Matrix metalloproteinase (MMP) 13 (collagenase 3) is poised to play a crucial role in bone formation and remodeling because of its expression both in terminal hypertrophic chondrocytes in the growth plate and in osteoblasts. Moreover, a mutation in the human MMP13 gene causes the Missouri variant of spondyloepimetaphyseal dysplasia. Inactivation of Mmp13 in mice through homologous recombination led to abnormal skeletal growth plate development. Chondrocytes differentiated normally but their exit from the growth plate was delayed. The severity of the Mmp13- null growth plate phenotype increased until about 5 weeks and completely resolved by 12 weeks of age. Mmp13-null mice had increased trabecular bone, which persisted for months. Conditional inactivation of Mmp13 in chondrocytes and osteoblasts showed that increases in trabecular bone occur independently of the improper cartilage ECM degradation caused by Mmp13 deficiency in late hypertrophic chondrocytes. Our studies identified the two major components of the cartilage ECM, collagen type II and aggrecan, as in vivo substrates for MMP13. We found that degradation of cartilage collagen and aggrecan is a coordinated process in which MMP13 works synergistically with MMP9. Mice lacking both MMP13 and MMP9 had severely impaired endochondral bone, characterized by diminished ECM remodeling, prolonged chondrocyte survival, delayed vascular recruitment and defective trabecular bone formation (resulting in drastically shortened bones). These data support the hypothesis that proper ECM remodeling is the dominant rate-limiting process for programmed cell death, angiogenesis and osteoblast recruitment during normal skeletal morphogenesis.

Animals↗
PubMed2004

Relationships of loading history and structural and material characteristics of bone: development of the mule deer calcaneus.

If a bone's morphologic organization exhibits the accumulated effects of its strain history, then the relative contributions of a given strain stimulus to a bone's development may be inferred from a bone's hierarchical organization. The artiodactyl calcaneus is a short cantilever, loaded habitually in bending, with prevalent compression in the cranial (Cr) cortex, tension in the caudal (Cd) cortex, and shear in the medial and lateral cortices (i.e., neutral axis). Artiodactyl calcanei demonstrate unusually heterogeneous structural and material organization between these cortices. This study examines potential relationships between developmental morphologic variations and the functional strain distribution of the deer calcaneus. One calcaneus was obtained from each of 36 (fetus to adult) wild deer. Predominant collagen fiber orientation (CFO), microstructural characteristics, mineral content (% ash), and geometric parameters were determined from transversely cut segments. Radiographs were examined for arched trabeculae, which may reflect tension/compression stress trajectories. Results showed that cross-sectional shape changes with age from quasi-circular to quasi-elliptical, with the long axis in the cranial-caudal direction of habitual bending. Cranial ("compression") cortical thickness increased at a greater rate than the Cd ("tension") cortex. Fetal bones exhibited arched trabeculae. Percent ash was not uniform (Cr > Cd), and this disparity increased with age (absolute differences: 2.5% fetuses, 4.3% adults). Subadult bones showed progressively more secondary osteons and osteocyte lacunae in the Cr cortex, but the Cd cortex tended to have more active remodeling in the subadult and adult bones. Nonuniform Cr:Cd CFO patterns first consistently appear in the subadults, and are correlated with secondary bone formation and habitual strain mode. Medial and lateral cortices in these groups exhibited elongated secondary osteons. These variations may represent "strain-mode-specific" (i.e., tension, compression, shear) adaptations. The heterogeneous organization may also be influenced by variations in longitudinal strain magnitude (highest in the Cr cortex) and principal strain direction-oblique in medial-lateral cortices (where shear strains also predominate). Other factors such as local reductions in longitudinal strain may influence the increased remodeling activity of the Cd cortex. Some structural variations, such as arched trabeculae, that are established early in ontogeny may be strongly influenced by genetic- or epigenetic-derived processes. Material variations, such as secondary osteon population densities and CFO, which appear later, may be products of extragenetic factors, including microdamage.

Age Factors↗
PubMed2006

Matricellular proteins: Extracellular modulators of bone development, remodeling, and regeneration.

Matricellular proteins are components of the extracellular matrix which are highly expressed in the developing and mature skeleton. Members of this protein class serve as biological mediators of cell function by interacting directly with cells or by modulating the activity of growth factors, proteases, and other extracellular matrix proteins. Although skeletons of matricellular protein-null mice are grossly normal, they each display unique deficiencies that are often magnified under pathological conditions. In addition, bone cells from wild-type and matricellular protein-null mice behave differently in various in vitro models of bone matrix synthesis and turnover. In this review, osteopontin, bone sialoprotein, tenascin C, SPARC, and thrombospondins 1 and 2 will each be discussed in the context of bone cell biology. Because the biological effects of matricellular proteins are largely context dependent, in vivo and in vitro results must be considered together in order to fully appreciate the specific contributions that matricellular proteins make to bone physiology and pathophysiology. In particular, it is clear that although matricellular proteins are not required for bone development and function, the proteins act to modulate post-natal bone structure in response to aging, ovariectomy, mechanical loading, and bone regeneration.

Animals↗
PubMed1990

Effect of feeding isoniazid and cimetidine on growth and bone development in male broiler chicks.

Because previous studies indicated that cimetidine (CIMET) and isoniazid (ISON) may inhibit vitamin D metabolism in both rats and humans, experiments were conducted to evaluate the influence of these drugs on growth and bone development in male broiler chicks. Chicks were fed a corn and soybean meal basal diet containing various levels of the drugs for 21 days. Body weight gain (BWG), feed consumption per bird (FB), tibia ash (TA), tibia breaking force (TBF), and plasma calcium levels were measured. In birds fed a diet supplemented with 1,100 ICU D3/kg, CIMET at up to 300 ppm resulted in a significant linear decrease in TA as the drug level increased. Birds fed ISON up to 405 ppm had inconsistent responses in TA and TBF. Body weight gain was only depressed with the highest level of ISON (405 ppm). The effects of feeding 0, 150, or 300 ppm CIMET were also investigated when chicks were fed 200 or 1,000 ICU per kg vitamin D3. The interaction between vitamin D3 and CIMET was significant for BWG, FCB, TA, and TBF. These were significantly reduced as the CIMET level increased for birds fed the low vitamin D3 diet but were not significantly affected when fed the high D3 diet. In another study in which chicks were fed a diet with 1,100 ICU vitamin D3, lowering the dietary Ca, or P, or both did not result in any effect of CIMET on the chicks. The results indicate that CIMET possibly interferes with normal bone formation in chicks by altering vitamin D3 metabolism.

Animals↗
PubMed2005

TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro.

UNLABELLED: We identified cellular targets of canonical Wnt signaling within the skeleton, which included chondrocytes, osteoblasts, and osteocytes in growing bone, but only osteocytes and chondrocytes in the mature skeleton. Mechanical deformation induced Wnt signaling in osteoblasts in vitro. INTRODUCTION: Genetic evidence in mice and humans has implicated the canonical Wnt signaling pathway in the control of skeletal development and bone mass. However, little is known of the details of Wnt signaling in the skeleton in vivo. We used Wnt indicator TOPGAL mice to identify which cells activated this pathway during bone development and in the mature skeleton. MATERIALS AND METHODS: We examined canonical Wnt signaling during embryonic and neonatal bone development in TOPGAL mice. The TOPGAL transgene consists of a beta-galactosidase gene driven by a T cell factor (TCF)beta-catenin responsive promoter so that canonical Wnt activity can be detected by X-gal staining. Expression of Wnt signaling components was examined in primary calvarial cell cultures by RT-PCR. The effect of mechanical deformation on Wnt signaling was examined in primary calvarial cells grown on collagen I and stretched using Flexercell Tension Plus System FX-4000T. Immunohistochemistry was used to examine the localization of beta-catenin in cartilage, bone, and cultured calvarial cells exposed to physical deformation. RESULTS AND CONCLUSIONS: Canonical Wnt signaling was active in several cell types in the fetal and neonatal skeleton, including chondrocytes, osteoblasts, and osteocytes. With age, activation of Wnt signaling became less prominent but persisted in chondrocytes and osteocytes. Although osteoblasts in culture expressed many different individual Wnt's and Wnt receptors, the TOPGAL transgene was not active in these cells at baseline. However, Wnt signaling was activated in these cells by physical deformation. Together with the activation of canonical Wnt signaling in osteocytes seen in vivo, these data suggest that Wnt signaling may be involved in the coupling of mechanical force to anabolic activity in the skeleton.

Animals↗
PubMed2001

Parathyroid hormone-related protein is required for normal intramembranous bone development.

It is well established that parathyroid hormone-related protein (PTHrP) regulates chondrocytic differentiation and endochondral bone formation. Besides its effect on cartilage, PTHrP and its major receptor (type I PTH/PTHrP receptor) have been found in osteoblasts, suggesting an important role of PTHrP during the process of intramembranous bone formation. To clarify this issue, we examined intramembranous ossification in homozygous PTHrP-knockout mice histologically. We also analyzed phenotypic markers of osteoblasts and osteoclasts in vitro and in vivo. A well-organized branching and anastomosing pattern was seen in the wild-type mice. In contrast, marked disorganization of the branching pattern of bone trabeculae and irregularly aligned osteoblasts were recognized in the mandible and in the bone collar of the femur of neonatal homozygous mutant mice. In situ hybridization showed that most of the osteoblasts along the bone surfaces of the wild-type mice and some of the irregularly aligned osteoblastic cells in the homozygous mice expressed osteocalcin. Alkaline phosphatase (ALP) activity and expression of osteopontin messenger RNA (mRNA) in primary osteoblastic cells did not show significant differences between cultures derived from the mixture of heterozygous mutant and wild-type mice (+/? mice) and those from homozygous mutant mice. However, both mRNA and protein levels of osteocalcin in the osteoblastic cells of homozygous mutant mice were lower than those of +/? mice, and exogenous PTHrP treatment corrected this suppression. Immunohistochemical localization of characteristic markers of osteoclasts and ruffled border formation did not differ between genotypes. Cocultures of calvarial osteoblastic cells and spleen cells of homozygous mutant mice generated an equivalent number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear and multinucleated cells and of pit formation to that of +/? mice, suggesting that osteoclast differentiation is not impaired in the homozygous mutant mice. These results suggest that PTHrP is required not only for the regulation of cartilage formation but also for the normal intramembranous bone development.

Adenosine Triphosphatases↗
PubMed1989

Spatial and temporal expression pattern of retinoic acid receptor genes during mouse bone development.

Spatial and temporal expression pattern of retinoic acid receptor (RAR) genes was investigated in mouse finger bones during development by an in situ hybridization method with riboprobes synthesized from a human cDNA of the RAR-alpha. We found that the RAR genes are expressed intensively and specifically in calcifying fronts of the mouse finger bones, whereas the expression pattern is rather uniform in the limb buds and cartilage matrices of the embryonic fingers. Our findings are consistent with the fact that vitamin A is essential for normal mammalian bone development.

Animals↗
PubMed1988

Dietary lactose improves endochondral growth and bone development and mineralization in rats fed a vitamin D-deficient diet.

Lactose promotes the intestinal absorption of calcium independent of the vitamin D endocrine system. The purpose of this study was to determine the effect of lactose supplementation on endochondral bone growth, bone development and mineralization in weanling rats fed a vitamin D-deficient diet. Rat pups were weaned from vitamin D-deficient dams and fed a vitamin D-deficient diet containing sucrose as the primary carbohydrate source or a similar diet but containing 20% lactose. After 4 wk, body weights, serum calcium levels and endochondral bone elongation rates in the lactose-fed animals were higher than in rats fed the sucrose diet. In addition, bone weights, bone calcium content, percent bone ash of bone dry weight, percent metaphyseal osseous tissues and bone osteoid content in the lactose-fed rats were different from those in the rats fed the sucrose diet. In all cases the changes in osseous tissues that were observed in the animals fed the lactose-supplemented diet were toward normal values as observed in age-matched animals fed a vitamin D-replete diet. The improvements in bone growth and development due to lactose supplementation occurred independent of the vitamin D endocrine system and are likely the result of improved calcium absorption in the intestine.

Animals↗
PubMed2006

Insulin-like growth factor-I is essential for embryonic bone development.

Although IGF-I has been identified as an important growth factor for the skeleton, the role of IGF-I on embryonic bone development remains unknown. Here we show that, in IGF-I-deficient (IGF-I(-/-)) mice, skeletal malformations, including short-limbed dwarfism, were evident at days post coitus (dpc) 14.5 to 18.5, accompanied by delays of mineralization in the spinal column, sternum, and fore paws. Reduced chondrocyte proliferation and increased chondrocyte apoptosis were identified in both the spinal ossification center and the growth plate of long bones. Abnormal chondrocyte differentiation and delayed initiation of mineralization was characterized by small size and fewer numbers of type X collagen expressing hypertrophic chondrocytes and lower osteocalcin expression. The Indian hedgehog-PTHrP feedback loop was altered; expression of Indian hedgehog was reduced in IGF-I(-/-) mice in long bones and in the spine, whereas expression of PTHrP was increased. Our results indicate that IGF-I plays an important role in skeletal development by promoting chondrocyte proliferation and maturation while inhibiting apoptosis to form bones of appropriate size and strength.

Animals↗
PubMed2005

Localization of Indian hedgehog and PTH/PTHrP receptor expression in relation to chondrocyte proliferation during mouse bone development.

We have developed a useful approach to examine the pattern of gene expression in comparison to cell proliferation, using double in situ hybridization and immunofluorescence. Using this system, we examined the expression of Indian hedgehog (Ihh) and PTH/PTHrP receptor (PPR) mRNA in relation to chondrocyte proliferation during embryonic mouse bone development. Both genes are expressed strongly in prehypertrophic and early hypertrophic chondrocytes, and there is a strong correlation between upregulation of both Ihh and PPR expression and chondrocyte cell cycle arrest. At embryonic day (E14.5), PPR mRNA upregulation begins in the columnar chondrocytes just prior to cell cycle exit, but at later time points expression is only observed in the postproliferative region. In contrast, Ihh mRNA expression overlaps slightly with the region of columnar proliferating chondrocytes at all stages. This study provides further evidence that in the developing growth plate, cell cycle exit and upregulation of Ihh and PPR mRNA expression are coupled.

Animals↗
PubMed1998

Role of PTHrP and PTH-1 receptor in endochondral bone development.

Parathyroid hormone-related peptide (PTHrP) has important functions in the control of cellular growth and differentiation. Acting, at least in part, through the PTH-1 receptor, PTHrP profoundly influences chondrocytic and osteogenic cell biology. Studies using knockout and transgenic mouse technology have played a pivotal role in unraveling the physiological role of PTHrP and its receptor in endochondral bone development and adult skeletal homeostasis. Further clarification of these functions will have far-reaching implications in our general understanding of skeletogenesis and the pathophysiology of human skeletal disorders.

Animals↗