Osteoinductive factor inhibits formation of human osteoclast-like cells

A. Kukita, Lynda Bonewald, D. Rosen, S. Seyedin, G. R. Mundy, G. David Roodman

Research output: Contribution to journalArticle

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Abstract

Osteoinductive factor (OIF) is a glycoprotein in bone that induces ectopic bone formation. Implantation of OIF plus transforming growth factor β (TGF-β) type 1 or 2 into subcutaneous tissues of rats induces formation of bone at the implantation site. Since TGF-β 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 towage. 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-β 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-β, 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.

Original languageEnglish (US)
Pages (from-to)3023-3026
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number8
StatePublished - Apr 1990
Externally publishedYes

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Osteoclasts
Transforming Growth Factors
Bone Matrix
Osteogenesis
Bone and Bones
Subcutaneous Tissue
Prostaglandins
Intercellular Signaling Peptides and Proteins
Glycoproteins
Bone Marrow
Monoclonal Antibodies
Phenotype
Antibodies

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Osteoinductive factor inhibits formation of human osteoclast-like cells. / Kukita, A.; Bonewald, Lynda; Rosen, D.; Seyedin, S.; Mundy, G. R.; Roodman, G. David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 8, 04.1990, p. 3023-3026.

Research output: Contribution to journalArticle

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AU - Bonewald, Lynda

AU - Rosen, D.

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AU - Mundy, G. R.

AU - Roodman, G. David

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AB - Osteoinductive factor (OIF) is a glycoprotein in bone that induces ectopic bone formation. Implantation of OIF plus transforming growth factor β (TGF-β) type 1 or 2 into subcutaneous tissues of rats induces formation of bone at the implantation site. Since TGF-β 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 towage. 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-β 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-β, 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.

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