ENCRYPTED MORPHOGENS OF SKELETOGENESIS - BIOLOGICAL ERRORS AND PHARMACOLOGICAL POTENTIALS

Bone morphogenetic proteins (BMPs) are members of a class of ancient, highly conserved signalling molecules that play major roles in embryon ic axis determination, organ development, tissue repair, and regenerat ion 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, an d recombinant proteins have been produced for many of these genes. Tra nsgenic and naturally occurring animal models demonstrate a wide varie ty 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 oss ificans progressiva (FOP), a rare and devastating genetic disease of e ctopic osteogenesis in humans, is associated with over-expression of a t least one of the BMPs. The BMPs, their transmembrane receptors, thei r intracellular signal transducers, and their secreted antagonists hol d great promise as pharmacologic agents in modulating a vast array of developmental and regenerative pathways in human diseases. (C) 1998 El sevier Science Inc.