INITIATION AND PROMOTION OF BONE DIFFERENTIATION BY BONE MORPHOGENETIC PROTEINS

The presence of growth and differentiation factors in bone has been de monstrated by subcutaneous implantation of demineralized bone matrix t hat initiates new cartilage and bone morphogenesis. The genes for bone morphogenetic proteins (BMPs) have been cloned and expressed. Recombi nant BMPs induce endochondral bone formation in vivo. The multistep se quential developmental cascade consists of chemotaxis, mitosis, and di fferentiation of cartilage and bone. The pleiotropic response has been well characterized. BMPs stimulate osteogenic and chondrogenic phenot ypes. Natural bovine osteogenin (BMP-3) and recombinant BMP-4 are equi potent in chemotaxis, limb bud chondrogenesis, cartilage maintenance, and in vivo bone induction. There are multiple isoforms of BMPs, raisi ng the biologic relevance of the redundancy. The mode of action and se cond messengers are not dear. BMPs appear to have cognate receptors as demonstrated by iodinated BMP-2B (BMP-4). Other novel members of the BMP family include osteogenic protein 1 (BMP-7) and osteogenic protein 2 (BMP-8). Bone morphogenetic proteins are members of the transformin g growth factor-beta superfamily and include three distinct subfamilie s: BMP-2, BMP-3, and BMP-7. Native BMP-3 and recombinant BMP4 bind typ e IV collagen of the basement membrane. This novel connection may be t he long elusive mechanistic explanation for the requirement of angioge nesis and vascular invasion for bone morphogenesis. BMPs may have a ro le in fracture repair, periodontal regeneration, and alveolar ridge au gmentation.