Growth factors for bone growth and repair: IGF, TGF beta and BMP

Current research is reviewed regarding the actions of three growth factor systems on bone formation: insulin-like growth factors (IGFs), transforming growth factor-betas (TGF betas), and bone morphogenetic proteins (BMPs). Each growth factor family consists of multiple related growth factor genes. TGF betas and BMPs 2-7 are subfamilies of a larger TGF beta superfamily. IGFs, TGF betas and BMPs are produced by osteoblasts and other bone cells and affect osteoblast proliferation and differentiation. They are also incorporated into mineralized bone matrix and retain activity when extracted from bone. Various hormones, growth factors, and mechanical stress influence bone cell production of IGFs, TGF betas, and BMPs. Thus these growth factors may function in local regulation of bone formation. Currently there is much interest in the function of IGF binding proteins, which are also produced by bone cells, in regulating IGF activities in bone. Recently, mechanisms for activation of the TGF beta serine/threonine kinase receptors have been investigated, and receptors for BMPs have been identified which are structurally related to TGF beta receptors. In vivo studies are discussed which demonstrate the applicability of IGFs, TGF betas and BMPs to increasing bone formation systemically, promoting fracture healing and inducing bone growth around implants.