Regulation of tenascin-C expression in bone cells by transforming growth factor-beta.
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.
Mackie
E J
EJ
School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia. e.mackie@vet.unimelb.edu.au
Abraham
L A
LA
Taylor
S L
SL
Tucker
R P
RP
Murphy
L I
LI
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis; D010294:Parietal Bone / Q000187:drug effects; D012886:Skull / Q000187:drug effects* / Q000378:metabolism; D019063:Tenascin / Q000032:analysis / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D019063:Tenascin; D016212:Transforming Growth Factor beta