Opposite effects of bone morphogenetic protein-2 and transforming growth factor-beta 1 on osteoblast differentiation

Several members of the transforming growth factor-beta (TGF-beta) superfami ly have been demonstrated to play regulatory roles in osteoblast differenti ation and maturation, but the mechanisms by which they act on different cel ls at different developmental stages remain largely unknown. We studied the effects of TGF-beta1 and bone morphogenetic protein-2 (BMP-2) on the diffe rentiation/maturation of osteoblasts using the murine cell lines MC3T3-E1 a nd C3H10T1/2. BMP-2 induced or enhanced the expression of the osteoblast di fferentiation markers alkaline phosphatase (ALP) and osteocalcin (OC) in bo th cells. In contrast, TGF-beta1 was not only unable to induce these marker s, but it dramatically inhibited BMP-2-mediated OC gene expression and ALP activity. In addition, TGF-PI inhibited the ability of BMP-2 to induce MC3T 3-E1 mineralization. TGF-beta1 did not sensibly modify the increase of Osf2 /Cbfal gene expression mediated by BMP-2, thus demonstrating that the inhib itory effect of TGF-beta1 on osteoblast differentiation/maturation mediated by BMP-2 was independent of Osf2/Cbfa1 gene expression. Finally, it is sho wn that TGF-beta1 does not affect BMP-2-induced Smad1 transcriptional activ ity in the mesenchymal pluripotent cells studied herein. Our data indicate that in vitro BMP-2 and TGF-beta1 exert opposite effects on osteoblast diff erentiation and maturation. (C) 2001 by Elsevier Science Inc. All rights re served.