AbstractIt has been shown that bone cells produce and secrete several growth factors (GFs) which are also found in the bone matrix. To investigate the role of these growth factors in bone cell metabolism, we compared the effects of different factors separately and in combination with respect to osteoblastic cell proliferation and differentiation. While basic fibroblast GF (FGF), transforming GFβ-1 (TGFβ), and platelet-derived GF (PDGF) enhance DNA synthesis, they had the opposite effect on alkaline phosphatase (ALP) activity in cell extracts: FGF, TGFβ, and PDGF inhibited cell ALP but strongly stimulated DNA synthesis. The IGFs had little effect on cell ALP but increased the release of ALP into the conditioned medium. In mitogenic tests of combinations of GFs, most had at least additive effects at low concentrations, and FGF, TGFβ, and IGF2 produced synergistic effects. Evidence is presented for (1) the modulation of the effects of one GF by the action of other GF, (2) synergistic interactions between FGF, TGFβ, and IGF2, and (3) a possible role for the observed interactions among GF for the mitogenic effect of human bone extract.