Using collagenase-induced osteoarthritis (CIOA) model in mice, where synovial hyperplasia and the effect of macrophages were more pronounced with significant synovial activation [9], our study elucidates the mechanistic role of NOD2 in orchestrating the activation of synovial macrophages, and highlights NOD2 as a potential target for OA prevention and treatment. The gene discussed is NOD2; the disease is osteoarthritis.