The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide.
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.
Rheumatology Division, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, Boston, MA 02115, USA. mgoldrin@bidmc.harvard.edu
Mary B
MB
Goldring
Francis
F
Berenbaum
D000818:Animals; D019902:Chondrocytes / Q000502:physiology*; D003094:Collagen / Q000235:genetics; D051546:Cyclooxygenase 2; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D047495:PPAR gamma / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology
D018836:Inflammation Mediators; D007527:Isoenzymes; D008565:Membrane Proteins; D047495:PPAR gamma; D011453:Prostaglandins; D009569:Nitric Oxide; D003094:Collagen; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases