Abstract
Within the mature articular cartilage matrix, which has no blood or nerve supply, chondrocytes show little metabolic activity with low turnover of matrix components. Under conditions of stress because of biomechanical factors, however, chondrocytes are capable of producing mediators that are associated with inflammation, including cytokines such as interleukin-1 and tumor necrosis factor-alpha, which in turn stimulate the production of prostaglandins and nitric oxide. Chondrocytes also express receptors for these mediators, which accumulate at high local concentrations and can act in an autocrine-paracrine fashion to feedback-regulate chondrocyte responses. Prostaglandin E2 can exert catabolic or anabolic effects depending on the microenvironment. Nitric oxide can promote cellular injury and increase chondrocyte susceptibility to cytokine-induced apoptosis. Because cross-talk between these mediators produces complex modulation of catabolic and anabolic pathways, further studies in vitro and in vivo are required to elucidate their precise roles in osteoarthritis.