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 and function of osteoblasts, the cells responsible for bone formation. One approach is the targeted expression of designer G protein-coupled receptors (GPCRs) that exhibit controlled signaling through specific G protein pathways. Initial results using two such designer GPCRs indicate that Gs signaling in osteoblasts positively regulates a potent anabolic pathway whereas Gi signaling results in osteoporosis. Analysis of the osteoblast transcriptome in these models has identified candidate mediators of anabolic and anti-anabolic signaling. We have also found that blockade of Gi signaling in osteoblasts in vivo protects female mice from age-related bone loss. We are currently testing the possibility that factors produced in the local bone marrow environment are responsible for initiating Gi signaling in osteoblasts thereby inhibiting bone loss in aging females. We have also initiated a series of studies to define the pathways responsible for heterotopic bone formation associated with BMP signaling and trauma. Specifically, we are testing the idea that endothelial cells migrate to the injury site and serve as the source of osteoprogenitors.