NOS inhibition reverses TLR2-induced chondrocyte dysfunction

Ping Shen et al. from Max Löhning’s group at DRFZ and Charité – Universitätsmedizin Berlin show that degradation products of extracellular matrix (ECM) of joint cartilage stimulate Toll-like receptors (TLR) on chondrocytes from osteoarthritis patients. These TLR signals trigger a cartilage-degenerative program through induction of nitric oxide synthase-2 (NOS2). The degeneration program is characterized by reduced metabolic and cartilage-anabolic activities and enhanced inflammatory and cartilage-catabolic functions in human chondrocytes. NOS inhibition largely reversed these effects, and Nos2 gene deficiency protected mice from age-related osteoarthritis. Thus, TLR signaling acts as a putative driver of chondrocyte dysfunction in osteoarthritis through nitric oxide induction.