Articular cartilage destruction in synovial joints is one of the key features of osteoarthritis (OA). This destruction has long been thought to be the result of wear and tear injuries. Although, some studies have shown the presence of low-grade inflammation in the joints of OA patients, its exact role in the pathogenesis of OA has been unclear so far. A recent study conducted by American scholars suggests that complement may play a key role in the onset and development of OA. First, researchers studying human specimens found abnormally high levels of complement activation in synovial fluid and synovial tissue specimens from OA patients. Animal studies further showed that mice defective in complement C5, C6 or the complement regulatory protein CD59a gene were less likely to have the histopathological manifestations of OA and had a better functional prognosis. For example, in the unstable joints of C5-deficient mice, the levels of inflammatory mediators and degradative molecules in chondrocytes were lower than in mice without C5 deficiency. It is suggested that complement may play an important role in the pathogenesis of OA. This study also suggests that one possible mechanism by which complement mediates structural damage in OA joints is that complement components C5-9 can form membrane attack complexes (MACs). The latter can directly cause chondrocyte damage and upregulate the activation of other inflammatory pathways in the joint. Evidence for this includes: MAC induces inflammatory cytokine and degradative molecules in chondrocytes cultured in vitro; MAC coexists with matrix metalloproteinase 13 (MMP13); and MAC coexists with extracellular signal-regulated kinase (ERK) activated around chondrocytes in OA patients. The researchers concluded that abnormal complement levels within the synovial joint and its associated cascade response may be one of the key factors in the pathogenesis of OA, with the potential to develop new therapies for OA that target the complement system in the future.