Nitric Oxide in Arthritis: It’s Probably There But What’s It Doing?
Arthritis is a disease of diarthrodial joints. Although some forms of arthritis involve extraarticular tissues, the most prominent pathological lesions occur within the joints and all forms of arthritis produce articular inflammation or cartilage destruction or both. Patients with osteoarthritis (OA), for example, suffer considerable loss of cartilage with only low levels of inflammation, whereas the joints of patients with systemic lupus erythematosus (SLE; lupus) do not lose cartilage, despite being highly inflamed. Extensive cartilage loss and high levels of inflammation occur together in the joints of patients with rheumatoid arthritis (RA). In considering the possible roles of nitric oxide (NO) in arthritis, it is thus necessary to determine how NO influences both inflammation and cartilage erosion within joints. As these are distinct pathophysiological processes (Evans 1995a) they could respond differently to NO.
KeywordsNitric Oxide Articular Cartilage Synovial Fluid Nitric Oxide Production Articular Chondrocytes
Unable to display preview. Download preview PDF.
- Albina JE, Abate JA, Henry WL (1991) Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-y in the induction of the nitric oxide-synthesizing pathway. J Immunol 147: 144–148Google Scholar
- Amin AR, DiCesare PE, Vyas P, Attur M, Tzeng E, Billiar TR, Stuchin SA, Abramson SB (1995a) The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase. J Exp Med 182: 2097–2102PubMedCrossRefGoogle Scholar
- Brown Z, Robson RL, Westwick J (1993) L-arginine/nitric oxide pathway: a possible signal transduction omechanism for the regulation of the chemokine IL-8 in human mesangial cells. In: Lindley IJD, Westwick J, Kunkel S (eds) The chemokines: biology of the inflammatory peptide supergene family II. Adv Exp Med Biol 351: 65–75Google Scholar
- Cao M, Westerhausen-Larson A, Niyibizi C, Kavalkovich K, Georgescu HI, Rizzo CF, Hebda PA, Stefanovic-Racic M, Evans CH (1997) Nitric oxide inhibits the synthesis of type II collagen without altering COL2A I mRNA abundance: prolyl hydroxylase as a possible target. Biochem J 324: 305–310PubMedGoogle Scholar
- DeCaterina R, Libby P, Peng HB, Thannickai VJ, Rajavashisth TB, Gimbrone MA, Shin WS, Liao JK (1995) Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 96: 60–68Google Scholar
- Evans CH (1995a) Cartilage loss. In: Kuettner KE, Goldberg VM (eds) Osteoarthritic disorders. American Academy of Orthopaedic Surgeons, Rosemont, p 271Google Scholar
- Evans CH (1997) Synovium. In: Dee R (ed) Principles of orthopaedic practice, 2nd edn. McGraw-Hill, New York, pp 99–108Google Scholar
- Evans CH (1996) Nitric oxide and inflammation. In: Faist E, Baue AE, Schildberg FW (eds) The immune consequences of trauma, shock and sepsis. Pabst Science Publishers, Berlin, p 640 (Mechanisms and therapeutic approaches, vol 1 )Google Scholar
- Gregory SH, Wing EJ, Hoffman RA, Simmons RL (1993) Reactive nitrogen intermediates suppress the primary immunological response to Listeria. J Immunol 150: 29901–2909Google Scholar
- Häuselmann HJ, Stefanovic-Racic M, Künzli S, Michel BA, Evans CH (1997) The role of nitric oxide in proteoglycan synthesis and catabolism by superficial and deep layers of human articular cartilage (submitted for publication )Google Scholar
- Hung GL, Evans CH (1994) Synovium. In: Fu FH, Harper CD, Vince KG (eds) Knee surgery. Williams and Wilkins, Baltimore, pp 141–154Google Scholar
- Jacobs T, Morrell M, Manzi S, Verdile V, Simmons RL (1992) Elevated nitrates in inflammatory joint disease: nitric oxide in arthritis (abstract). Arthritis Rheum 35 [Suppl]: R9Google Scholar
- Kaur H, Halliwell B (1994) Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett 350: 9–12Google Scholar
- Schumacher HR, Klippel JH, Koopman WJ (eds) (1993) Primer on the rheumatic diseases, 10th edn. Arthritis Foundation, AtlantaGoogle Scholar
- Stefanovic-Racic M, Georgescu HI, Evans CH (1994a) Effects of anti-arthritic drugs upon the production of nitric oxide by rabbit synoviocytes and chondrocytes (abstract). Arthritis Rheum 37 [Supp1]: S386Google Scholar
- Stefanovic-Racic M, Möllers M, Miller LA, Evans CH (1997) Nitric oxide and proteoglycan turnover in rabbit articular cartilage. J Orthop Res (In Press)Google Scholar
- Weinberg JB, Granger DL, Pisetsky DS, Seldin MF, Misukonis MA, Mason SN, Pippen AM, Ruiz P, Wood ER, Gildeson GS (1994) The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-1pr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine. J Exp Med 179: 651–660PubMedCrossRefGoogle Scholar