"Pathological bone loss (osteolysis), the process whereby osteoclasts erode mineralised bone matrix, remains an unresolved challenge in the pathology of osteolytic diseases, such as osteoporosis, rheumatoid arthritis (RA) and osteolytic bone cancers. Identification of the receptors involved in osteoclast development (osteoclastogenesis) is currently a high priority in osteoclast research. The goal of this research is to identify and understand the receptors and ligands regulating osteoclastogenesis. The primary aim of this proposal is to identify how these osteoclastogenic signals operate in osteolytic diseases. OSCAR is an osteoclast receptor that delivers potent osteoclastogenic signals. I have discovered that type I-IV collagens (major structural proteins at sites of diseased joint and bone erosion) are ligands for OSCAR and drive osteoclastogenesis. This exciting new finding has changed our understanding of the environmental signals regulating osteoclastogenesis. I will use gene knockouts, mouse and human disease models to dissect the molecular interactions required for osteoclastogenesis using OSCAR as a model receptor/ligand interaction. Using these techniques, I will determine the role of the OSCAR, and other receptors, in osteoclastogenesis in vivo and in the diseased state."