Kukita A, Bonewald L, Rosen D, Seyedin S, Mundy G R, Roodman G D
Research Service and Geriatric Research, Education and Clinical Center, Audie Murphy Veterans Administration Hospital, San Antonio, TX.
Proc Natl Acad Sci U S A. 1990 Apr;87(8):3023-6. doi: 10.1073/pnas.87.8.3023.
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.
骨诱导因子（OIF）是一种存在于骨中的糖蛋白，可诱导异位骨形成。将OIF与转化生长因子β（TGF-β）1型或2型植入大鼠皮下组织可诱导植入部位形成骨。由于TGF-β也存在于骨基质中，且在长期人骨髓培养中可抑制表达破骨细胞表型的多核细胞形成，因此我们测试了OIF对这些破骨细胞样细胞形成的影响，以确定OIF对破骨细胞谱系细胞的作用。我们发现，OIF以剂量依赖的方式抑制总多核细胞（MNC）形成，并优先抑制与单克隆抗体23c6（23c6阳性MNC）反应的MNC形成，23c6是一种识别破骨细胞的抗体。此外，低浓度的OIF与低浓度的TGF-β联合作用可协同抑制23c6阳性MNC形成。OIF对23c6阳性MNC形成的抑制作用不是由前列腺素合成介导的。这些数据表明，储存在骨基质中并在骨吸收时释放的调节性生长因子，如OIF或TGF-β，可通过抑制破骨细胞形成而作为破骨细胞活性的天然抑制剂。
