Non-coordinate control of bone formation displayed by growth factor combinations with IGF-I

Polypeptide growth factors (GFs) promote osteogenesis by enhancing the mitogenesis, migration, and matrix synthesis of osteoblasts. Most previous investigators have evaluated only the effects of single GFs on these parameters. Studies on single GFs might overlook large biological responses comparable with those documented in the cell cycle literature when GFs are used in combinations that interact synergistically. Ln this study, we screened for synergistic interactions between IGF-I and three additional GFs (PDGF-BB, TGF-beta 1, and bFGF) on the regulation of bone growth and differentiation. Fetal bovine osteoblasts were assessed for osteoblast mitogenesis, collagenous and non-collagenous protein synthesis, and alkaline phosphatase activity (ALP). Our results show synergistic interactions between IGF-I and the other GFs on osteoblast mitogenic activity and protein synthesis. In contrast to synergistic mitogenic and protein synthesis effects, IGF-I failed to increase ALP activity when combined with TGF-beta 1, PDGF-BB, and bFGF in bovine osteoblast-like cells.