The expression level of NOD2 in human osteoarthritis (OA) cartilage is significantly higher than that of normal cartilage, and its combined action with TLR2 contributes to the pro-catabolic gene expression induced by 29-kDa amino terminal (matrix degradation product in synovial fluid of patients with OA) in human chondrocytes.431,432 This indicates that the NOD2 and TLR2 cross-regulatory pathway may be a target to prevent the development of arthritis. This evidence concerns the gene NOD2 and osteoarthritis.