[RESEARCH ON THE DEVELOPMENT OF THE BONES OF MOUSE EXTREMITIES. STUDY IN VIVO AND IN ORGAN-TYPE CULTURE IN VITRO].
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Animals↗
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Results for “Bone Development”
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[How is the interaction between cartilage and subchondral bone during development and joint pathology?].
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Animals↗
Estrogen receptors alpha and beta are differentially expressed in developing human bone.
Estrogen plays an essential role in the development and maintenance of the skeleton; its effects are mediated via interactions with two estrogen receptor (ER) subtypes, alpha and beta. The aim of this study was to establish the cellular distribution of ERalpha and ERbeta in neonatal human rib bone. ERalpha and ERbeta immunoreactivity was seen in proliferative and prehypertrophic chondrocytes in the growth plate, with lower levels of expression in the late hypertrophic zone. Different patterns of expression of the two ERs were seen in bone. In cortical bone, intense staining for ERalpha was observed in osteoblasts and osteocytes adjacent to the periosteal-forming surface and in osteoclasts on the opposing resorbing surface. In cancellous bone, ERbeta was strongly expressed in both osteoblasts and osteocytes, whereas only low expression of ERalpha was seen in these areas. Nuclear and cytoplasmic staining for ERbeta was apparent in osteoclasts. These observations demonstrate distinct patterns of expression for the two ER subtypes in developing human bone and indicate functions in both the growth plate and mineralized bone. In the latter, ERalpha is predominantly expressed in cortical bone, whereas ERbeta shows higher levels of expression in cancellous bone.
Bone Development↗
Spontaneous growth and bone age development in a patient with 17alpha-hydroxylase deficiency: evidence of the role of sexual steroids in prepubertal bone maturation.
A male pseudohermaphrodite with 17alpha-hydroxylase deficiency and complete nonvirilization was monitored for excessive weight from the age of 3.5 to 11.5 years before the absence of sex steroids was detected. The retrospective analysis of growth data showed retarded bone age development despite adequate growth, which led to a remarkable increase in final height prognosis.
Adolescent↗
Development of bone canaliculi during bone repair.
We recently found that silver impregnation staining with protargol (silver protein), that is, a modified Bodian method, is useful for histologically identifying the details of bone canaliculi structure, using thin sections of decalcified bone tissues. With this staining method, we conducted the present study to assess the development of bone canaliculi during the process of intramembranous ossification using a fracture-like stimulation model of the rat femur. After making a drill-hole in the cortex of the rat femur, decalcified thin sections were obtained after 3, 5, 7, and 14 days by the standard paraffin-embedding procedure. Silver staining for bone canaliculi was performed using our previously reported technique. The results showed that woven bone covered the fracture surface of the cortex after 5 days, then immature lamellar bone attached to the woven bone after 7 days, and finally the lamellar bone matured and became thick with appositional growth after 14 days. The osteocytes in the woven bone appeared at an early stage of bone repair and developed a few canaliculi that were short and irregularly distributed in the osteoid matrix, while the osteocytes in the lamellar bone at a late stage formed many bone canaliculi that were long and regularly distributed in mature bone matrix. Therefore, we concluded that woven bone osteocytes may be necessary for induction of the lamellar bone osteocytes followed by active appositional growth of the lamellar bone at the early stage of bone repair, and also that both bone tissues could be clearly distinguished from one another based on the pattern of development of bone canaliculi by the osteocytes, as seen with the use of our sensitive staining method.
Animals↗
Regulation of bone cell development and function: implication for renal osteodystrophy.
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Bone Development↗
Skeletal development in premature infants: a review of bone physiology beyond nutritional aspects.
Bone development is usually seen as a process of bone mineral accretion or increase in bone mass, and treatment of bone disorders usually consists of attempts to maximise bone mass accumulation by nutritional means only. However, from a functional perspective, bones should not be as heavy as possible, but rather as stable as necessary. It is therefore important to create conditions that stimulate bones to become more stable.
Bone Development↗
Early manifestation of type 1 diabetes in children is a risk factor for changed bone geometry: data using peripheral quantitative computed tomography.
OBJECTIVE: Normal to severely decreased bone mineral density has been reported in children with type 1 diabetes. To detect possible abnormalities in bone mineralization, geometry, and muscle bone unit, we measured selective parameters in children with type 1 diabetes using peripheral quantitative computed tomography. METHODS: Measurements of the radius by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics as well as muscle mass in 88 patients (42 girls, 46 boys) at a mean age of 11.7 +/- 3.0 years, a mean disease duration of 5.6 +/- 3.7 years, and a mean manifestation age of type 1 diabetes of 6.1 +/- 3.5 years. Height, weight, Tanner stage, insulin regimen, and glycosylated hemoglobin values were recorded. Bone metabolism was studied by measurement of bone formation and bone resorption parameters. Dynamic muscle force was measured using a grip strength device. RESULTS: Overall, cortical, trabecular, and total bone mineral density were within the reference range. Total and cortical bone cross-sectional area and muscle mass were low in prepubertal patients, and total cross-sectional area was low in early puberty. Adolescent patients showed normal bone and muscle parameters. Grip strength and recreational physical activity were normal in all in relation to a healthy reference population. In a subgroup of 18 patients, early manifestation of type 1 diabetes was detected as a risk factor for altered bone development with significantly reduced cortical bone mineral density and total, cortical, and muscle cross-sectional area (-0.9 +/- 1.3 SD, -2.1 +/- 1.3 SD, -1.6 +/- 0.7 SD, and -1.0 +/- 0.7 SD, respectively). Bone characteristics were not influenced by metabolic control, disease duration, or insulin regimen. CONCLUSIONS: Manifestation of type 1 diabetes at an early age may impair bone development. Longitudinal data are needed to determine whether this impairment persists into adolescence and adulthood.
Adolescent↗
Activity and distribution of lysosomal enzymes during collagenous matrix-induced cartilage, bone, and bone marrow development.
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Acid Phosphatase↗
Marrow stromal cells from patients affected by MPS I differentially support haematopoietic progenitor cell development.
Bone marrow transplantation is the therapy of choice in patients affected by MPS I (Hurler syndrome), but a high incidence of rejection limits the success of this treatment. The deficiency of alpha-L-iduronidase (EC 1.2.3.76), one of the enzymes responsible for the degradation of glycosaminoglycans, results in accumulation of heparan and dermatan sulphate in these patients. Heparan sulphate and dermatan sulphate are known to be important components of the bone marrow microenvironment and critical for haematopoietic cell development. In this study we compared the ability of marrow stromal cells from MPS I patients and healthy donors to support normal haematopoiesis in Dexter-type long term culture. We found an inverse stroma/supernatant ratio in the number of clonogenic progenitors, particularly the colony-forming unit granulocyte-machrophage in MPS I cultures when compared to normal controls. No alteration in the adhesion of haematopoietic cells to the stroma of MPS I patients was found, suggesting that the altered distribution in the number of clonogenic progenitors is probably the result of an accelerated process of differentiation and maturation. The use of alpha-L-iduronidase gene-corrected marrow stromal cells re-established normal haematopoiesis in culture, suggesting that correction of the bone marrow microenvironment with competent enzyme prior to transplantation might help establishment of donor haematopoiesis.
Adolescent↗
[Murine leukemia virus Akv promotes bone tumor development in fos-transgenic mice].
Newborn hMT-fos-LTR transgenic C3H mice and their non-transgenic siblings were infected with Akv, derived from the ecotropic provirus of the AKR mouse. Bone sarcomas in non-infected transgenics were observed in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. Akv-infected transgenics developed bone tumors with higher frequency and at younger age: Females in 69% (20/28) at 268 +/- 122 days, males in 83% (24/29) at 279 +/- 109 days. In the majority of the bone tumors of Akv-infected transgenics (70% in females, 59% in males) cellular atypia was lacking and the histological pattern resembled human parosteal osteosarcoma. Only 50% (12/24) of bone tumors in Akv-infected transgenics revealed newly integrated virus sequences by Southern analysis. PCR analysis detected Akv sequences in DNAs of all tumors. Obviously, the insertion of Akv in a few cells induced the considerably accelerated bone tumor growth.
Animals↗
Transgenic expression of the EXT2 gene in developing chondrocytes enhances the synthesis of heparan sulfate and bone formation in mice.
Hereditary multiple exostoses (HME), a dominantly inherited disorder characterized by multiple cartilaginous tumors, is caused by mutations in the gene for, EXT1 or EXT2. Recent studies have revealed that EXT1 and EXT2 are required for the biosynthesis of heparan sulfate and exert maximal transferase activity as a complex. The Drosophila homologue of EXT1 (tout-velu) regulates the movement and signaling of Hedgehog protein, which plays an important role in the regulation of chondrocyte differentiation and bone development. In this study, to investigate the biological role of EXT2 in bone development in vivo and the pathological role of HME mutations in the development of exostoses, we generated transgenic mice expressing EXT2 or mutant EXT2 in developing chondrocytes. Histological analyses and micro-CT scanning showed that the biosynthesis of heparan sulfate and the formation of trabeculae were upregulated in EXT2-transgenic mice, but not in mutant EXT2-transgenic mice. The expression of EXT1 is concomitantly upregulated in EXT2-transgenic and even mutant EXT2-transgenic mice, suggesting an interactive regulation of EXT1 and EXT2 expression. These findings support that the EXT2 gene encodes an essential component of the glycosyltransferase complex required for the biosynthesis of heparan sulfate, which may eventually modulate the signaling involved in bone formation.
Animals↗
Development of bone mineral density at the lumbar spine and femoral neck in juvenile chronic arthritis--a prospective one year followup study.
OBJECTIVE: To determine the magnitude of lumbar and femoral bone mineral gain in patients with juvenile chronic arthritis (JCA) using dual X-ray absorptiometry. METHODS: Bone mineral density (BMD) was measured at entry and again after 12 months at the lumbar spine and femoral neck in healthy children (n = 65) and children with oligoarticular (n = 36) and polyarticular (n = 69) JCA. Five of the oligoarticular and 38 polyarticular patients were treated with systemic glucocorticoids. In addition to the changes in BMD, the annual changes in calculated bone mineral volumetric density (BMDvol) and bone size were determined simultaneously. RESULTS: In polyarticular JCA, the acquisition of BMD was decreased at the femoral neck (2.2 vs 4.8%; p < 0.05), but remained the same at the spine compared with healthy children; in oligoarticular JCA, the increase in BMD at the femoral neck was similar to that in controls, but significantly increased at the spine compared with the change in the control group (7.4 vs 4.9%; p < 0.05). The detected annual changes in BMD were associated with the changes in BMDvol. Bone mineral gain was significantly delayed at the lumbar spine in children treated with glucocorticoids. CONCLUSION: In children with JCA, the development of bone mineral is different at the lumbar spine and at the femoral neck, but it also depends on the subtype of JCA and on the use of systemic glucocorticoids.
Adolescent↗
Expression of mRNA for IL1 beta, IL6 and TGF beta 1 in developing human bone and cartilage.
Using in situ hybridization, we investigated the expression of mRNA for interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and transforming growth factor-beta-1 (TGF beta 1) in sections of developing bone in human osteophytes. The expression was related to the cellular activity of alkaline phosphatase to aid in the identification of pre-osteoblast populations. IL1 beta mRNA was localized in active osteoblasts within distinct areas of intramembranous ossification. However, the expression was sporadic and appeared to occur at a specific stage of the osteoblast life cycle. There was no IL1 beta mRNA expression in any cell types during endochondral ossification. IL6 mRNA expression was located within pre-osteoblasts and in newly differentiated and matrix-secreting osteoblasts; expression was absent or reduced in flattened, inactive osteoblasts. Weak or no IL6 expression was observed in chondroblasts and chondrocytes, respectively. However, there was a close association between IL6 mRNA expression and the differentiation of mesenchymal cells into osteoblasts. TGF beta 1 expression was localized to osteoblasts apposed to bone or cartilage matrix; the intensity of expression correlated with matrix secretion. Chondroblasts and chondrocytes expressed lower but significant levels of TGF beta 1 mRNA; the expression was lost with the progression to calcifying cartilage. The three cytokines studied were differentially expressed both temporally and spatially, suggesting different roles for each in osteoblast and chondrocyte function.
Alkaline Phosphatase↗
Mepe is expressed during skeletal development and regeneration.
a bone metabolism regulator that is expressed by osteocytes in normal adult bone. Here, we used an immunohistochemical approach to study whether Mepe has a role in murine long bone development and regeneration. Our data showed that Mepe protein was produced by osteoblasts and osteocytes during skeletogenesis, as early as 2 days postnatal. During the healing of non-stabilized tibial fractures, which occurs through endochondral ossification, Mepe expression was first detected in fibroblast-like cells within the callus by 6 days postfracture. By 10 and 14 days postfracture (the hard callus phase of repair), Mepe was expressed within late hypertrophic chondrocytes and osteocytes in the regenerating tissues. Mepe became externalized in osteocyte lacunae during this period. By 28 days postfracture (the remodeling phase of repair), Mepe continued to be robustly expressed in osteocytes of the regenerating bone. We compared the Mepe expression profile with that of alkaline phosphatase, a marker of bone mineralization. We found that both Mepe and alkaline phosphatase increased during the hard callus phase of repair. In the remodeling phase of repair, Mepe expression levels remained high while alkaline phosphatase activity decreased. We also examined Mepe expression during cortical bone defect healing, which occurs through intramembranous ossification. Mepe immunostaining was found within fibroblast-like cells, osteoblasts, and osteocytes in the regenerating bone, through 5 to 21 days postsurgery. Thus, Mepe appears to play a role in both long bone regeneration and the latter stages of skeletogenesis.
Alkaline Phosphatase↗
Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development.
Bone morphogenetic proteins (BMPs) have been implicated in the regulation of ovarian follicular development and are promising candidates to apply in IVM and IVF protocols. We investigated the expression of BMP2, BMP4 and BMP receptors in bovine ovaries and the effects of BMP2 and BMP4 during oocyte maturation on bovine IVM. Reverse transcription polymerase chain reaction studies with antral follicles showed the expression of BMPR-IA, BMPR-IB, ActR-IA, ActR-IIB, BMPR-II and BMP4 mRNA in all follicular compartments, while BMP2 mRNA was generally restricted to theca and cumulus tissue. Immunohistochemistry demonstrated the presence of BMPR-II in oocytes and granulosa cells of preantral follicles but only in oocytes of antral follicles. The immunostaining of BMP2 and BMP4 was limited to theca interna and approximately 25% of oocytes of antral follicles. Exogenously added BMP2 or BMP4 to IVM medium did not affect oocyte nuclear maturation, cumulus cell expansion, nor blastocyst formation following IVF. It is concluded that a BMP-signaling system, consisting of BMP2, BMP4, type II and I receptors, is present in bovine antral follicles and that this system plays a role in development and functioning of these follicles rather than in final oocyte maturation and cumulus expansion.
Animals↗
Single dose 6 Gy prophylaxis for heterotopic ossification after total hip arthroplasty.
Forty-five patients (50 hips) at risk for heterotopic ossification after total hip arthroplasty who received a single dose of 6 Gy postoperative irradiation were compared with a historical control group of 42 patients (50 hips) with similar risk factors who did not receive radiation prophylaxis. All surgeries were done by the same surgeon using the same perioperative protocol. Radiation was delivered through anteroposterior/posteroanterior limited fields, avoiding areas of desired bony ingrowth. Of those hips that received radiation, Grade II or III heterotopic bone developed in 6% and Grade IV heterotopic bone developed in none. Of the control group, Grade II or III heterotopic bone developed in 34% of the hips and Grade IV heterotopic bone in 6%. The radiated hips had a significant net gain in abduction and adduction when compared with the nonradiated hips. No early complications were noted in association with the radiation treatment. A single dose of 6 Gy of radiation given within the first 3 postoperative days provides effective prophylaxis against heterotopic ossification developing after total hip arthroplasty in high risk patients.
Aged↗
Osteoclast development: the cell surface and the bone environment.
Bone development and remodelling processes depend on complex interactions between bone cell precursors, mature bone cells, extracellular matrix molecules, growth factors, the immune system and humoral factors. The exact molecular nature of many of the cell-cell and cell-matrix interactions occurring during bone remodelling remains to be resolved. Cell surface molecules are likely to have important roles in both bone cell differentiation and regulatory processes. However, little is known about changes in the osteoclast cell surface during development and there is only limited information on the cell surface composition of the mature cell phenotype. We describe how one osteoclast-specific monoclonal antibody has been used to identify, characterize and purify a 96 kDa/140 kDa osteoclast membrane protein. The antibody has also been used as a phenotypic marker in studies designed to identify soluble and matrix-related bone factors involved in the terminal stages of osteoclast differentiation. In parallel studies using marrow-derived giant cells and the chick chorioallantoic membrane (CAM), immunohistochemical and enzyme-linked immunoassays (ELISA) have been used to investigate the influence of calvaria, calvaria-conditioned medium, bone matrix, and bone matrix components on osteoclast development. Marrow-derived giant cells express osteoclast-specific cell surface antigens when co-cultured with live calvariae or when exposed to calvaria-conditioned medium. In the richly vascularized and mesenchymal cell-containing CAM, intact bone matrix induces the formation of giant cells that express the osteoclast-specific antigens. In contrast, isolated bone matrix components implanted on the CAM recruit only mononuclear cells which are not recognized by the osteoclast-specific antibody.
Animals↗