Signal transduction and biological functions of bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs) are multi-functional growth factors and belong to the transforming growth factor beta (TGFbeta) superfamily. The roles of BMPs in embryonic development and cellular functions in postnatal animals have been extensively studied in recent years. Signal transduction studies have revealed that Smad1 and 5 are the immediate downstream molecules of BMP receptor and play a central role in BMP signal transduction. Using transgenic and knockout approaches and animal models with naturally occurring mutations in BMP genes, it has been shown that BMPs play critical roles in mesoderm formation, heart development, cartilage development and postnatal bone formation. Recombinant BMP-2 and 7 have been used clinically for several different clinical interventions such as non-union fractures and spinal fusions. Tissue-specific knockout of a specific BMP ligand, a subtype of BMP receptors or a specific signaling molecule is required to further determine the specific role of a particular BMP ligand, receptor or signaling molecule.