Abstract
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.
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Selected References
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- Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
- Bentz H., Nathan R. M., Rosen D. M., Armstrong R. M., Thompson A. Y., Segarini P. R., Mathews M. C., Dasch J. R., Piez K. A., Seyedin S. M. Purification and characterization of a unique osteoinductive factor from bovine bone. J Biol Chem. 1989 Dec 5;264(34):20805–20810. [PubMed] [Google Scholar]
- Chenu C., Pfeilschifter J., Mundy G. R., Roodman G. D. Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5683–5687. doi: 10.1073/pnas.85.15.5683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frolik C. A., Dart L. L., Meyers C. A., Smith D. M., Sporn M. B. Purification and initial characterization of a type beta transforming growth factor from human placenta. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3676–3680. doi: 10.1073/pnas.80.12.3676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horton M. A., Lewis D., McNulty K., Pringle J. A., Chambers T. J. Human fetal osteoclasts fail to express macrophage antigens. Br J Exp Pathol. 1985 Feb;66(1):103–108. [PMC free article] [PubMed] [Google Scholar]
- Horton M. A., Lewis D., McNulty K., Pringle J. A., Chambers T. J. Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens. Cancer Res. 1985 Nov;45(11 Pt 2):5663–5669. [PubMed] [Google Scholar]
- Ignotz R. A., Endo T., Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987 May 15;262(14):6443–6446. [PubMed] [Google Scholar]
- Kukita T., McManus L. M., Miller M., Civin C., Roodman G. D. Osteoclast-like cells formed in long-term human bone marrow cultures express a similar surface phenotype as authentic osteoclasts. Lab Invest. 1989 Apr;60(4):532–538. [PubMed] [Google Scholar]
- Laiho M., Saksela O., Andreasen P. A., Keski-Oja J. Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta. J Cell Biol. 1986 Dec;103(6 Pt 1):2403–2410. doi: 10.1083/jcb.103.6.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDonald B. R., Mundy G. R., Clark S., Wang E. A., Kuehl T. J., Stanley E. R., Roodman G. D. Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures. J Bone Miner Res. 1986 Apr;1(2):227–233. doi: 10.1002/jbmr.5650010210. [DOI] [PubMed] [Google Scholar]
- MacDonald B. R., Takahashi N., McManus L. M., Holahan J., Mundy G. R., Roodman G. D. Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. Endocrinology. 1987 Jun;120(6):2326–2333. doi: 10.1210/endo-120-6-2326. [DOI] [PubMed] [Google Scholar]
- Masui T., Wakefield L. M., Lechner J. F., LaVeck M. A., Sporn M. B., Harris C. C. Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2438–2442. doi: 10.1073/pnas.83.8.2438. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeilschifter J., Chenu C., Bird A., Mundy G. R., Roodman G. D. Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res. 1989 Feb;4(1):113–118. doi: 10.1002/jbmr.5650040116. [DOI] [PubMed] [Google Scholar]
- Pfeilschifter J., Mundy G. R. Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2024–2028. doi: 10.1073/pnas.84.7.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roberts A. B., Anzano M. A., Meyers C. A., Wideman J., Blacher R., Pan Y. C., Stein S., Lehrman S. R., Smith J. M., Lamb L. C. Purification and properties of a type beta transforming growth factor from bovine kidney. Biochemistry. 1983 Dec 6;22(25):5692–5698. doi: 10.1021/bi00294a002. [DOI] [PubMed] [Google Scholar]
- Roodman G. D., Ibbotson K. J., MacDonald B. R., Kuehl T. J., Mundy G. R. 1,25-Dihydroxyvitamin D3 causes formation of multinucleated cells with several osteoclast characteristics in cultures of primate marrow. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8213–8217. doi: 10.1073/pnas.82.23.8213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyedin S. M., Segarini P. R., Rosen D. M., Thompson A. Y., Bentz H., Graycar J. Cartilage-inducing factor-B is a unique protein structurally and functionally related to transforming growth factor-beta. J Biol Chem. 1987 Feb 15;262(5):1946–1949. [PubMed] [Google Scholar]
- Seyedin S. M., Thomas T. C., Thompson A. Y., Rosen D. M., Piez K. A. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2267–2271. doi: 10.1073/pnas.82.8.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sporn M. B., Roberts A. B., Shull J. H., Smith J. M., Ward J. M., Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. doi: 10.1126/science.6572416. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Kukita T., MacDonald B. R., Bird A., Mundy G. R., McManus L. M., Miller M., Boyde A., Jones S. J., Roodman G. D. Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures. J Clin Invest. 1989 Feb;83(2):543–550. doi: 10.1172/JCI113916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi N., MacDonald B. R., Hon J., Winkler M. E., Derynck R., Mundy G. R., Roodman G. D. Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures. J Clin Invest. 1986 Oct;78(4):894–898. doi: 10.1172/JCI112677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi N., Yamana H., Yoshiki S., Roodman G. D., Mundy G. R., Jones S. J., Boyde A., Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988 Apr;122(4):1373–1382. doi: 10.1210/endo-122-4-1373. [DOI] [PubMed] [Google Scholar]
- Tashjian A. H., Jr, Levine L. Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Commun. 1978 Dec 14;85(3):966–975. doi: 10.1016/0006-291x(78)90638-1. [DOI] [PubMed] [Google Scholar]
- Tashjian A. H., Jr, Voelkel E. F., Lazzaro M., Goad D., Bosma T., Levine L. Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism. Endocrinology. 1987 May;120(5):2029–2036. doi: 10.1210/endo-120-5-2029. [DOI] [PubMed] [Google Scholar]
- Tashjian A. H., Jr, Voelkel E. F., Lazzaro M., Singer F. R., Roberts A. B., Derynck R., Winkler M. E., Levine L. Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4535–4538. doi: 10.1073/pnas.82.13.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wrann M., Bodmer S., de Martin R., Siepl C., Hofer-Warbinek R., Frei K., Hofer E., Fontana A. T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J. 1987 Jun;6(6):1633–1636. doi: 10.1002/j.1460-2075.1987.tb02411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]