Encrypted morphogens of skeletogenesis: biological errors and pharmacologic potentials.

Bone morphogenetic proteins (BMPs) are members of a class of ancient, highly conserved signalling molecules that play major roles in embryonic axis determination, organ development, tissue repair, and regeneration throughout the animal kingdom. The bone morphogenetic proteins are potent developmental morphogens that act in a concentration-dependent manner to specify cell fates in developing and regenerating systems. Complementary DNAs have been cloned for approximately twenty BMPs, and recombinant proteins have been produced for many of these genes. Transgenic and naturally occurring animal models demonstrate a wide variety of potential functions for BMP genes during development and tissue regeneration, and a wide range of pharmacologic effects are predicted from knock-out or over-expression of the BMP genes. Fibrodysplasia ossificans progressiva (FOP), a rare and devastating genetic disease of ectopic osteogenesis in humans, is associated with over-expression of at least one of the BMPs. The BMPs, their transmembrane receptors, their intracellular signal transducers, and their secreted antagonists hold great promise as pharmacologic agents in modulating a vast array of developmental and regenerative pathways in human diseases.