Grant: Operating Grant

Osteoporosis, arthritis and periodontitis are high prevalence bone lytic diseases in which pathological bone loss is a central determinant of disease progression. These diseases are associated with considerable morbidity and place heavy burdens on the health care system as a result of pathologic fractures, joint destruction and tooth loss, respectively. Osteoclasts are multi-nucleated cells that resorb bone during both normal bone turnover but their bone resorptive activity is increased in pathological bone diseases. The activity and size of osteoclasts is regulated by the fusion of osteoclast progenitor cells. Consequently, defining the regulation of cell fusion leading to osteoclast formation is critical for developing novel therapeutic approaches for high prevalence bone lytic diseases. We have identified an actin filament severing protein, adseverin, which mediates the formation of cell protrusions that are required for the fusion step of osteoclastogenesis. By understanding how this protein regulates osteoclast formation during inflammation we may be able to develop treatments that prevent this process directly thereby identifying new therapeutic approaches.