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At least 343 records · Page 19Linked to original sources
PubMed1999

In vivo expression of transcripts encoding the Glvr-1 phosphate transporter/retrovirus receptor during bone development.

In vitro observations suggest that inorganic phosphate (Pi) transport plays an important functional role in osteogenic cells and in their matrix vesicles for the initiation of matrix calcification. Recent studies have shown that the type III sodium-dependent Pi transporters, Glvr-1 and Glvr-2, are expressed in human osteoblast-like cells and have suggested a potential role for type III transporters in regulated Pi handling in osteogenic cells. To address the relevance of these findings in the context of bone formation in vivo and, in particular, in relation to matrix calcification, we investigated expression of the Glvr-1 transporter by in situ hybridization in developing embryonic murine metatarsals, using human Glvr-1 cDNA as a probe. In this model of endochondral ossification, expression of transcripts encoding Glvr-1 could be detected from day 17 of embryonic development. A hybridization signal for Glvr-1 was specifically observed in a subset of hypertrophic chondrocytes and could not be detected in osteoblasts. The expression of Glvr-1 mRNA was compared with that of transcripts encoding extracellular matrix proteins. Glvr-1 mRNA expression was confined to a population of early hypertrophic chondrocytes expressing type X collagen and to slightly more mature cells that express transcripts encoding osteopontin but lack type X collagen mRNA. No Glvr-1 transcripts were detected in fully differentiated hypertrophic chondrocytes. This pattern of Glvr-1 mRNA expression was maintained throughout embryonic development until after birth. In conclusion, the Glvr-1 phosphate transporter is selectively expressed in a subset of hypertrophic chondrocytes during endochondral bone formation, in a region where matrix mineralization proceeds. This observation represents the first in vivo evidence consistent with a potential role for this phosphate transporter in matrix calcification.

Animals↗
PubMed2000

Human Dermo-1 has attributes similar to twist in early bone development.

Basic helix-loop-helix (bHLH) transcription factors are implicated in cell lineage determination and differentiation. Dermo-1 encodes a bHLH transcription factor that shares extensive homology with another bHLH transcription factor, Twist. We have cloned and characterized human Dermo-1 from two different bone cytoplasmic DNA (cDNA) libraries. Dermo-1 mRNA and protein expression were examined in human embryo and adult tissue sections. Dermo-1 is expressed in a subset of mesodermally and ectodermally derived tissues. We further examined expression of Dermo-1/Twist in human tissues and cell lines. In addition, we observed Dermo-1 expression in response to basic fibroblast growth factor in osteoblastic cell lines. To evaluate the functionality of the human Dermo-1 transcription factor in osteoblast metabolism, we made stable osteoblastic cell lines that over- and underexpress human Dermo-1. These cell lines were analyzed and compared with previously published data of similar cell lines transfected with Twist. Our results demonstrate that Dermo-1 caused changes similar to Twist in the osteogenic properties of osteoblastic cells, such as morphology, bone marker gene expression, and biochemical response to cytokines. However, Dermo-1 expression also has unique effects in regulating the mechanism of proliferation, on alkaline phosphatase enzyme activity, and in temporal expression patterns. We speculate that expression of Twist and Dermo-1 maintains cells in an osteoprogenitor or preosteoblast-like state, respectively, and prevents premature or ectopic osteoblast differentiation. Therefore, Twist and Dermo-1 must be sequentially downregulated in order to initiate the cascade of events responsible for osteogenic cell differentiation. These results indicate that, during osteoblast development, Dermo-1 may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype by utilizing mechanisms similar but not identical to those utilized by Twist.

Amino Acid Sequence↗
PubMed2001

Establishment and characterization of a cell line from a malignant fibrous histiocytoma of bone developing in a patient with multiple fibrous dysplasia.

PURPOSE AND METHODS: In order to provide material for genetic analysis of fibrous dysplasia (FD), a cell line designated GBS-1 was established from a secondary bone malignant fibrous histiocytoma (MFH) developing in a rib of a 44-year-old male polyostotic FD patient. RESULTS: The GBS-1 cells are characterized by a pleomorphic spindle cell morphology with abundant mucus production. On transplantation to nude mouse subcutis the cell line forms myxoid-spindle cell sarcomas with giant cells, the myxoid product being positive for periodic acid-Schiff (PAS) and alcian blue (Al-B) stains and completely digested by hyaluronidase, mimicking the original tumor. Chromosome and genetic analyses revealed multiple structural and numerical abnormalities of chromosomes with a large number of unidentifiable chromosomes and p53 mutation in exon 7 with LOH in the counterpart. CONCLUSIONS: Since cell lines for FD have hitherto not been available, the GBS-1 cells should prove useful for genetic analyses of FD and also MFH of bone origin.

Adult↗
PubMed2002

Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization.

The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been established to control skeletal tissue formation and biomineralization via the regulation of gene expression. This action involves the well-characterized nuclear 1,25(OH)2D3 receptor. However, it has been recognized that several cellular responses to 1,25(OH)2D3 may not to be related to the exclusive nuclear receptor. Indeed, this secosteroid is able to generate rapid responses that have been proposed to be mediated by interactions of the ligand, which is a putative cell membrane-associated rapid-response steroid (MARRS) binding protein for 1,25(OH)2D3 [1,25D3-MARRS]. The nongenomic pathway of 1,25(OH)2D3 was studied here in detail by immunolocalization of the 1,25D3-MARRS during the specific context of human prenatal development. Western blotting with proteins extracted from 4 week- to 27-week-old embryos was performed, evidencing a 65-kDa molecular species recognized by antibody Ab 099 generated against synthetic peptides corresponding to the N terminus of the 1,25D3-MARRS from chick intestinal basolateral membranes. Based on this biochemical conservation of protein in the human species, the temporospatial expression patterns were established in the craniofacial skeleton at the same ages. Comparative analysis was performed in teeth and bones from early morphogenesis to terminal cell differentiation and extracellular biomineralization. The data show the potential implication of 1,25D3-MARRS in the heterogeneous cell population including ameloblasts, odontoblasts, osteoblasts, and osteoclasts. The epithelial-mesenchymal cascade related to odontogenesis was coincident with a sequence of up- and down-regulation of immunoreactive 1,25D3-MARRS. Biomineralization was associated with a striking up-regulation in the adjoining secretory cells in all tissues. Finally, osteoclasts appeared also to express the 1,25D3-MARRS during these early phases of bone modeling. Previously obtained data of the nuclear vitamin D receptor (VDR) expression and this study on 1,25D3-MARRS suggest the existence of cross-talk between the genomic and nongenomic pathways during human development.

Ameloblasts↗
PubMed2004

Cathepsin L-deficient mice exhibit abnormal skin and bone development and show increased resistance to osteoporosis following ovariectomy.

The role of cathepsin L in normal physiological processes was assessed using cathepsin L homozygous knockout mice (B6;129-Ctsl(tm1Alpk)). These mice were generated using gene targeting in embryonic stem cells. Null mice fail to express mRNA and protein to cathepsin L. They developed normally and were fertile. The distinct phenotypic change exhibited was a progressive hair loss, culminating in extensive alopecia by 9 months of age. Histological analysis of the skin from homozygous mice revealed diffuse epithelial hyperplasia, hypotrichosis, hair shaft fragmentation and utricle formation. These findings provide evidence that cathepsin L is involved in the regulation of epithelial cell proliferation and differentiation in the skin. In addition, the role of cathepsin L in bone remodelling was evaluated. Using bone histomorphometric measurements, trabecular, but not cortical, bone volume was found to be significantly decreased in the cathepsin L heterozygote and homozygote mice compared to the wild-type mice. Following ovariectomy, it was observed that loss of trabecular bone, the most metabolically active component of bone, occurred to a lesser extent in homozygote, and heterozygote mice, than was seen in wild-type mice. These observations suggest that cathepsin L is likely to have a role in controlling bone turnover during normal development and in pathological states.

Animals↗
PubMed1995

A new technique for measurements on long bones: development of a new instrument and techniques comparison.

In this paper we present a new instrument for measurements on long bones. The instrument is based on the use of a digital coordinatometer-goniometer connected to an optical collimator: such device allows angles as well as lengths to be measured. With regard to observing procedures, an innovative method for bone axis location by points has been applied. It is also possible to locate an axis using a symmetry and tangency criterion. As for torsion angles, the proposed technique is absolutely new; it utilizes a reference plane, which the bone must be leaned against, and the symmetry conditions that are generated by rotating the bone around an axis orthogonal to this plane. In order to verify the precision of the new instrument (digital osteogoniometer), several tests were performed. For this purpose we have studied the results of measurements carried out with the new instrument as well as with traditional apparatuses by four different observers on a sample of 10 skeletons (humerus, radius, ulna, femur, tibia of left side). The analysis of intrapersonal and interpersonal differences points out that the new osteogoniometer is more precise in angular measurements than traditional instruments. Moreover the time requested for carrying out measurements prooved to be shorter, above all with regard to torsion angles measurements.

Adult↗
PubMed1995

Galectin-3 is expressed in the notochord, developing bones, and skin of the postimplantation mouse embryo.

The galectins are a family of low molecular weight, calcium-independent mammalian carbohydrate binding proteins that exhibit specificity for beta-galactoside derivatives. We have examined the expression pattern of galectin-3 in the developing mouse embryo by in situ hybridisation and immunohistochemistry. In the embryo proper, galectin-3 message and protein are first detected in notochord, starting from 8.5 days post coitum (dpc), and persist until this structure disappears. Galectin-3 is later found in cartilage primordia and in developing skin from 13.5 dpc. This very restricted and dynamic pattern suggests that galectin-3 may participate in the establishment and/or maintenance of notochord as well as the formation of cartilage and differentiation of skin. Finally, we find that galectin-3, which is identical to the macrophage marker Mac-2, is also expressed in embryonic macrophages.

Animals↗
PubMed1998

The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation.

During vertebrate limb development, growth plate chondrocytes undergo temporally and spatially coordinated differentiation that is necessary for proper morphogenesis. Parathyroid hormone-related peptide (PTHrP), its receptor, the PTH/PTHrP receptor, and Indian hedgehog are implicated in the regulation of chondrocyte differentiation, but the specific cellular targets of these molecules and specific cellular interactions involved have not been defined. Here we generated chimeric mice containing both wild-type and PTH/PTHrP receptor (-/-) cells, and analyzed cell-cell interactions in the growth plate in vivo. Abnormal differentiation of mutant cells shows that PTHrP directly signals to the PTH/PTHrP receptor on proliferating chondrocytes to slow their differentiation. The presence of ectopically differentiated mutant chondrocytes activates the Indian hedgehog/PTHrP axis and slows differentiation of wild-type chondrocytes. Moreover, abnormal chondrocyte differentiation affects mineralization of cartilaginous matrix in a non-cell autonomous fashion; matrix mineralization requires a critical mass of adjacent ectopic hypertrophic chondrocytes. Further, ectopic hypertrophic chondrocytes are associated with ectopic bone collars in adjacent perichondrium. Thus, the PTH/PTHrP receptor directly controls the pace and synchrony of chondrocyte differentiation and thereby coordinates development of the growth plate and adjacent bone.

Animals↗
PubMed1989

Osteoinduction: a report on the discovery and research of unique protein growth factors mediating bone development.

Osteoinductive factor, a unique glycoprotein, is the latest growth factor to be discovered. When combined with transforming growth factor-beta 1 or transforming growth factor-beta 2, osteoinductive factor can stimulate the formation of endochondral bone in a collagen-ceramic composite. Preliminary laboratory studies indicate a wide potential for the use of osteoinductive products in orthopedics, oral reconstruction, and periodontal procedures.

Bone Morphogenetic Proteins↗
PubMedDate not supplied

Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development.

Fibromodulin, a keratan-sulfate proteoglycan, was first isolated in articular cartilage and tendons. We have identified fibromodulin as a gene regulated during BMP-2-induced differentiation of a mouse prechondroblastic cell line. Because expression of fibromodulin during endochondral bone formation has not been studied, we examined whether selected cells of the chondrocytic and osteoblastic lineage expressed fibromodulin. Fibromodulin mRNA was detected in conditionally immortalized murine bone marrow stromal cells, osteoblasts, and growth plate chondrocytes, as well as in primary murine calvarial osteoblasts. We, therefore, investigated the temporo-spatial expression of fibromodulin in vivo during endochondral bone formation by in situ hybridization. Fibromodulin was first detected at 15.5 days post coitus (dpc) in the perichondrium and proliferating chondrocytes. Fibromodulin mRNA was also detected at 15.5 dpc in the bone collar and periosteum. At later time points fibromodulin was expressed in the primary spongiosa and the endosteum. To determine whether fibromodulin was expressed during intramembranous bone formation as well, in situ hybridization was performed on calvariae. Fibromodulin mRNA was present in calvarial osteoblasts from 15.5 dpc. These results demonstrate that fibromodulin is developmentally expressed in cartilage and bone cells during endochondral and intramembranous ossification. These findings suggest that this extracellular matrix protein plays a role in both endochondral and intramembranous bone formation.

Animals↗