The objective of the project is to investigate the role of growth and differentiation factors in bone and cartilage development and repair. Special emphasis is placed on initiation factors in bone development. Osteogenin (Bone Morphogenetic Protein-3) is a prototype of such a differentiation initiation factor. The projects currently under investigation with salient findings are: 1) expression of cartilage phenotype by osteogenin; 2) stimulation of chick limb bud cell-induced cartilage differentiation and matrix synthesis by recombinant human Bone Morphogenetic Protein-2B; 3) influence of osteogenin on chondrocytes; 4) expression of insulin-like growth factor II receptor during endochondral bone differentiation; 5) identification of receptors by chemical crosslinking of recombinant bone morphogenetic protein to osteoblastic cells; 6) osteogenin is chemotactic for monocytes, and 7) repair of massive calvarial defects in primates. The above investigations have direct implications for correction of craniofacial and periodontal defects and non-unions in orthopaedic surgery.