Osteoinductive factor inhibits formation of human osteoclast-like cells.

Abstract

Osteoinductive factor (OWF) is a glycoprotein in bone that induces ectopic bone formation. Implantation of OIF plus transforming growth factor (3 (TGF-(8) type 1 or 2 into subcutaneous tissues of rats induces formation of bone at the implantation site. Since TGF-(3 is also present in bone matrix and inhibits formation of multinucleated cells that express an osteoclast phenotype in long-term human marrow cultures, we tested the effects of OIF on formation of these osteoclast-like cells to determine the effects of OIF on cells in the osteoclast lineage. We found that OIF inhibited total multinucleated cell (MNC) formation in a dose-dependent fashion and preferentially inhibited formation of MNCs that react with monoclonal antibody 23c6 (23c6-positive MNCs), an antibody that identifies osteoclasts. In addition, low concentrations of OWF in combination with low concentrations of TGF-(3 acted synergistically to inhibit 23c6-positive MNC formation. The inhibition of 23c6-positive MNC formation by OWF was not mediated by prostaglandin synthesis. These data suggest that regulatory growth factors, such as OWF or TGF-(3, that are stored within the bone matrix and released when bone is resorbed can serve as natural inhibitors of osteoclast activity by inhibiting osteoclast formation.

Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair

“…Osteoglycin and osteoprotegerin (OPG, the soluble decoy receptor for OPGL or RANKL) both inhibit osteoclast formation, 27,28 and are likely expressed in an attempt to rescue destruction of the bone. Cartilage repair could be mediated by SPARC (osteonectin), an extracellular matrix protein involved in cartilage synthesis, which is overproduced by synovial cells from RA tissues.…”

Transcriptional Regulation by Transforming Growth Factor β of the Expression of Retinoic Acid and Retinoid X Receptor Genes in Osteoblastic Cells Is Mediated through AP-1

“…Thus, this cytokine may play a central role in the cytokine network of bone remodeling. In fact, many studies (5)(6)(7)(8)(9)(10)(11)(12) have demonstrated a functional role for this cytokine in the regulation of the proliferation and differentiation of osteoblastic and osteoclastic cells.…”

Gene expression profiling of articular cartilage reveals functional pathways and networks of candidate genes for osteochondrosis in pigs

“…3). Among these genes, lysyl oxidase (LOX), PDGFA, osteoglycin (OGN), and asporin (ASPN) regulate cartilage extracellular matrix synthesis and chondrogenesis (15,17,27,56). Moreover, we found that many DE genes in this network are directly or indirectly related to bone and cartilage metabolism, including interferon-␥ (IFNG) and transforming growth factor-beta 1 (TGF␤1).…”

“…OGN and ASPN belong to a family of small leucine-rich proteoglycans that contribute to the regulation of collagen fibrillogenesis and cellular growth, differentiation, and migration (63). OGN in combination with TGF-␤1 or 2 is effective in inhibiting osteoclast formation (27). ASPN is involved in cartilage extracellular matrix formation and binds to TGF-␤1 to inhibit TGF-␤-induced expression of cartilage matrix genes and chondrogenesis (26).…”