Bone morphogenetic protein signal transduction in bone.

Bone morphogenetic proteins (BMPs) promote bone formation by stimulating the proliferation and differentiation of osteoblasts. It has been suggested that non-union of the bone, and delayed healing, may be the result of decreased levels of BMP activity. Activation of BMP receptors initiates phosphorylation of the downstream effector proteins, known as receptor-regulated Smads, leading to signal transduction. Receptor-regulated Smads form a hetero-oligomeric complex with a common mediator Smad, which translocates into the nucleus and regulates target gene transcription. The BMP signalling cascade is closely regulated, with the inhibitory Smads blocking the intracellular signal cascade. Extracellular antagonists, such as noggin, inhibit binding to BMP receptors. BMP-2 and BMP-7 have demonstrated clinical utility for bone regeneration, and are commercially available through the use of recombinant DNA technology.