Inductive activity of recombinant human growth and differentiation factor-5

Growth and differentiation factor-5 (GDF-5) is a divergent member of the tr ansforming growth factor-beta/bone morphogenetic protein (BMP) superfamily that is required for proper skeletal patterning and development in the vert ebrate limb. Based on the homology of GDF-5 with other bane-inducing BR IP family members, the inductive activity of a recombinant form of human GDF-5 (rhGDF-5) was evaluated in a series of in vitro assays and in vivo bane-fo rmation models. The in vitro response to rhGDF-5 resulted in the formation of chondrogenic nodules in fetal rat calvarial cells cultured in the contex t of collagen or collagen/hyaluronate extracellular matrices. Matrices load ed with rhGDF-5 induced ectopic cartilaginous and osseous tissue when impla nted in subcutaneous or intramuscular sites. In nonhuman primate long-bone- defect and spinalfusion models, rhGDF-5 combined with a mineralized collage n matrix induced bone formation in a manner equivalent to autogenous bone. These results highlight the unique potential of rhGDF-5 in a wide variety o f orthopaedic applications.