Nitric oxide synthase and cyclooxygenase interactions in cartilage and meniscus: relationships to joint physiology, arthritis, and tissue repair.
Rheumatoid arthritis and osteoarthritis are painful and debilitating diseases with complex pathophysiology. There is growing evidence that pro-inflammatory cytokines (e.g., interleukin-1 and tumor necrosis factor alpha) and mediators (e.g., prostaglandins, leukotrienes, and nitric oxide) play critical roles in the development and perpetuation of tissue inflammation and damage in joint tissues such as articular cartilage and meniscus. While earlier studies have generally focused on cells of the synovium (especially macrophages), there is increasing evidence that chondrocytes and meniscal cells actively contribute to inflammatory processes. In particular, it is now apparent that mechanical forces engendered by joint loading are transduced to biological signals at the cellular level and that these signals modulate gene expression and biochemical processes. Here we give an overview of the interplay of cytokines and mechanical stress in the production of cyclooxygenases and prostaglandins; lipoxygenases and leukotrienes; and nitric oxide synthases and nitric oxide in arthritis, with particular focus on the interactions of these pathways in articular cartilage and meniscus.
Weinberg
J Brice
JB
Department of Medicine, Division of Hematology-Oncology, VA and Duke University Medical Centers, Durham, North Carolina 27705, USA. brice@duke.edu
Fermor
Beverley
B
Guilak
Farshid
F
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D019902:Chondrocytes / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008592:Menisci, Tibial / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D020370:Osteoarthritis, Knee / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012038:Regeneration; D015398:Signal Transduction; D013314:Stress, Mechanical; D013583:Synovial Membrane / Q000201:enzymology / Q000473:pathology
D018836:Inflammation Mediators; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases