Osteoinductive factor inhibits formation of human osteoclast-like cells.
Osteoinductive factor (OIF) is a glycoprotein in bone that induces ectopic bone formation. Implantation of OIF plus transforming growth factor beta (TGF-beta) type 1 or 2 into subcutaneous tissues of rats induces formation of bone at the implantation site. Since TGF-beta 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 OIF in combination with low concentrations of TGF-beta acted synergistically to inhibit 23c6-positive MNC formation. The inhibition of 23c6-positive MNC formation by OIF was not mediated by prostaglandin synthesis. These data suggest that regulatory growth factors, such as OIF or TGF-beta, 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.
Kukita
A
A
Research Service and Geriatric Research, Education and Clinical Center, Audie Murphy Veterans Administration Hospital, San Antonio, TX.
Bonewald
L
L
Rosen
D
D
Seyedin
S
S
Mundy
G R
GR
Roodman
G D
GD
D000527:Alprostadil / Q000032:analysis; D001846:Bone Development; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D015291:Transforming Growth Factors / Q000494:pharmacology
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C063488:OGN protein, human; D015291:Transforming Growth Factors; D002116:Calcitonin; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin