This chapter focuses on bone morphogenetic proteins (BMP), which are part of a large multigene family, the transforming growth factor β (TGF-β) superfamily, whose members are related to each other by relative degrees of sequence similarity but that possess a wide-ranging number of biological functions. Members of the BMP subfamily show an identifying pattern of seven conserved cysteine residues in the mature, carboxy-terminal portion of the protein, which is where BMP activity resides. Mature BMP proteins are synthesized as larger precursor molecules that are processed to approximately 30,000 molecular weight dimers before their secretion from the cell. Members of the BMP family initiate their cellular action by binding to transmembrane serine/theronine kinases known as type I and type II receptors. These closely related proteins are composed of a short cysteine-rich extracellular domain, a single transmembrane-spanning domain, and an intracellular domain with serine and theronine kinase regions. Once secreted, the availability of BMPs for receptor interactions is mediated by the presence of extracellular antagonists that appear to bind to BMP proteins and prevent their subsequent interaction with BMP receptors. Potential therapeutic applications for BMPs include replacement for bone grafting materials in orthopedic settings, replacing bone grafts for dental applications, and enhancing fixation of prosthetic metal implants.
