The objective of this project is to define the role of bone morphogenetic proteins in cartilage and bone formation, both in embryogenesis and in postnatal life. Our discovery that several bone morphogenetic proteins are included in the process of chondrocyte maturation and endochondral bone formation raises the question of the biological significance of their redundancy. To further define the function of bone morphogenetic proteins 3 and 7 we performed localization studies during human and mouse development by northern and in situ hybridization and immunocytochemistry, utilizing specific riboprobes, polyclonal and monoclonal antibodies. Both BMP-3 and 7 showed a specific localization pattern and were coordinately expressed during chondrogenesis, osteogenesis and development of basement membranes. The presence of BMPs in basement membranes was further elaborated by performing in vitro binding studies. High affinity binding of BMP-3, 4 and 7, and TGF-beta1 to collagen IV, suggested that type IV collagen may function as a TGF- beta superfamily affinity matrix. Lung and kidney were detected as major sites of production of BMP 3 and 7 respectively, suggesting broader physiological functions as their involvement in calcium homeostases. In view of this we intend to analyze their in vitro function during the process of chondrocyte maturation and in vivo regulation in the kidney and skeletal tissues in animal models with rickets, hypercalcaemia and uremia.
