Current research efforts in my laboratory are focused on the use of molecular and transgenic approaches to understand the influence of specific cellular signaling pathways on the differentiation of osteoblasts, the cells responsible for bone formation. We are using “designer” G protein-coupled receptors to asses the role of specific G protein signaling pathways in controlling osteoblastic bone formation in vivo and in vitro. Our recent results indicate that Gs signaling in osteoblasts is strongly coupled to increased bone formation whereas Gi signaling promotes bone loss (osteoporosis). These effects appear to be mediated by paracrine factors that are secreted by osteoblasts in response to G protein signaling. Current efforts are directed towards identifying these paracrine factors and determining how they regulate mesenchymal stem cell commitment to the osteoblast lineage and/or the differentiation of early osteoblasts. We are particularly interested in the paracrine regulation of the BMP and Wnt signaling pathways.