Transforming growth factor beta (TGFbeta) and factors in the extended TGFbeta family have profound effects on osteoclasts and osteoblasts. These factors, which include the newly described bone morphogenetic protein (BMP) family, are stored in the bone matrix. In this project, we plan to study constitutative expression of the available BMPs in cells of the osteoblast lineage, their regulation by estrogen, 1,25 dihydroxyvitamin D and retinoic acid, and correlation of expression of these factors with early growth response genes and other transcriptional factors. Our preliminary data suggest that there is a cascade of events involved in expression of BMPs by cells in the osteoblast lineage which begins with expression of the early growth response genes followed by expression of the BMPs. For these studies, we plan to use cultured fetal rat calvarial cells studied both during stages of proliferation and maturation, and human and rat osteosarcoma cells with the osteoblast phenotype. These studies should provide important information on the mechanism of local production of these factors In bone, and an understanding of how factors such as estrogen, 1,25 dihydroxyvitamin D and retinoic acid regulate bone resorption and bone formation through utilization of these bone-derived TGFbeta superfamily members.