Regulation of tenascin-C expression in bone cells by transforming growth factor-beta.

Abstract

Transforming growth factor-beta (TGF-beta) stimulates new bone formation when administered locally in vivo. The extracellular matrix protein tenascin-C, which is secreted by osteoblasts but absent from mineralized bone matrix, supports differentiation of cultured osteoblast-like cells. The current study was undertaken to determine whether expression patterns of tenascin-C in TGF-beta-treated bone cells are in agreement with a role for this protein as a mediator of TGF-beta-stimulated new bone formation. Expression of tenascin-C was investigated by immunohistochemistry in calvarial bones of mice to which TGF-beta had been locally administered. Three days after initiation of daily TGF-beta treatment, strong staining for tenascin-C was seen in regions where periosteal osteoprogenitor cells were undergoing proliferation in response to TGF-beta; by comparison, staining of periosteal surfaces of control bones was weak and discontinuous. Seven days after initiation of a course of five daily injections of TGF-beta, tenascin-C staining was still enhanced in treated bones. The ability of TGF-beta to regulate expression of tenascin-C in osteoblast-like cells in vitro was investigated using an osteosarcoma-derived cell line (ROS 17/2.8). TGF-beta caused a small but significant increase in secretion of tenascin-C into the medium, as determined by a solid phase dot immunoassay quantitated by densitometry. Western and northern blot analysis indicated that TGF-beta did not influence the pattern of expression of tenascin-C splice variants. These results indicate that TGF-beta stimulates osteoblastic tenascin-C expression and suggest that tenascin-C may act as a mediator of TGF-beta-induced new bone formation.