Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta.

We have tested the hypothesis that basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF beta) regulate the proliferation of osteoblast-like cells. Cells which migrated from central bone explants of fetal calf calvaria expressed markers characteristic of the osteoblast phenotype, including osteocalcin (bone Gla protein) secretion and increased cAMP production in response to treatment with PTH. Bone cells proliferated in response to bFGF in a dose- and time-dependent pattern (ED50 = 60 pg/ml media). bFGF increased both the rate of bone cell proliferation (1.7-fold above controls) and final cell density at confluence (3-fold above controls). Acidic FGF (aFGF) exerted comparable effects though with lesser potency (ED50 = 2 ng/ml). In addition to its mitogenic effect, bFGF increased the osteocalcin content of conditioned media, suggesting that bFGF also modulates the function of osteoblast-like cells. Although TGF beta did not stimulate bone cell proliferation, it potentiated the mitogenic effects of aFGF and bFGF. In the presence of bFGF (0.7 ng/ml) the response to TGF beta was dose-dependent (ED50 = 1.7 ng/ml), with maximal stimulation at 5 ng/ml. These results demonstrate that aFGF and bFGF are mitogenic for bone cells in vitro. Furthermore, TGF beta potentiates the effects of bFGF and aFGF on the proliferation of bone cells. Since these growth factors are present in bone tissue in vivo, these data support the proposal that FGF and TGF beta may participate in the regulation of bone formation.