Our research interests are focused on understanding the cellular and molecular mechanisms underlying inflammatory osteolysis. Human diseases such as erosive arthritis and aseptic loosening of orthopedic implants are complicated with inflammatory responses owing to infiltration of host defense cells including macrophages and osteoclasts culminating with elevated osteolysis. Thus, remedies to combat deterioration of bone directly should target the cells solely responsible for osteolysis, i.e. osteoclasts. We have several translational projects with immediate relevance to human osteolytic diseases. Specifically, we are investigating 1) mechanisms of particle induction of osteoclasts and osteolysis in response to orthopedic particles normally used in implants. 2) Molecular regulation of bone erosion in rheumatoid arthritis, and 3) molecular regulation of inflammatory osteoclastogenesis. We have determined that NF-kB and MAP kinases are the primary mechanisms underlying these inflammatory osteolytic diseases. Further, we have identified precise elements in the NF-kB pathway capable of regulating these osteolytic pathway and hold promise for therapeutic intervention.