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Celecoxib inhibits nitric oxide production in chondrocytes of ligament-damaged osteoarthritic rat joints

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Abstract

The purpose of this study was to demonstrate the direct effects of celecoxib, one of the selective cyclo-oxygenase (COX)-2 inhibitors, on nitric oxide (NO) and prostaglandinE2 (PGE2) synthesis in cultured osteoarthritic chondrocyte comparing with those of indomethacin. Articular chondrocytes were isolated from rat osteoarthritic knee joint with damaged anterior cruciate ligament and also from the sham knee joint. Chondrocytes were preincubated with or without IL-1 alpha, and were exposed to celecoxib, indomethacin (non-selective COX inhibitor), or nothing. The amounts of NO and PGE2 in culture supernatants of chondrocytes were measured by EIA or the Griess reaction. In a series of experiments preincubated with or without IL-1 alpha and exposed to nothing, PGE2 and NO levels were significantly higher in osteoarthritic chondrocytes than in sham chondrocytes. Celecoxib and indomethacin inhibited the increase of PGE2 in osteoarthritic chondrocytes. Celecoxib inhibited and indomethacin did not inhibit the increase of NO levels in osteoarthritic chondrocytes.

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References

  1. Smith WL, Garavito RM, Dewitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160

    Article  PubMed  CAS  Google Scholar 

  2. Mastbergen SC (2002) Selective COX-2 inhibition prevents proinflammatory cytokine-induced cartilage damage. Rheumatology 41:801–808

    Article  PubMed  CAS  Google Scholar 

  3. Mitchell JA, Akarasereenont P, Thiemermann C, Flower CRJ, Vane JR (1993) Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci USA 90:11693–11697

    Article  PubMed  CAS  Google Scholar 

  4. Brandt KD (1987) Nonsteroidal anti-inflammatory drugs and articular cartilage. J Rheumatol 14:132–133

    PubMed  CAS  Google Scholar 

  5. Pettipher ER, Henderson B, Edwards JC, HA Higgs (1989) Effects of indomethacin on swelling, lymphocyte influx and cartilage proteoglycan depletion in experimental arthritis. Ann Rheum Dis 48:623–627

    Article  PubMed  CAS  Google Scholar 

  6. EI Hajjaji H, Marcelis A, Devogelaer JP, Manicourt DH (2003) Celecoxib has a positive effect on the overall metabolism of hyaluronan and proteoglycans in human osteoarthritic cartilage. J Rheumatol 30:2444–2451

    PubMed  Google Scholar 

  7. Gilroy DW, Tomlinson A, Greenslade K, Speed MP, Willoughby DA (1998) The effects of cyclooxygenase-2 inhibitors on cartilage erosion and bone loss in a model of Mycobacterium tuberculosis-induced monoarticular arthritis in the rat. Inflammation 22:509–519

    Article  PubMed  CAS  Google Scholar 

  8. Hulth A, Lindberg L, Telhag H (1970) Experimental osteoarthritis in rabbits. Act Orthop Scandinav 41:522–530

    Article  CAS  Google Scholar 

  9. Kawiak J, Moskalewski S, Darzynkiewicz Z (1965) Isolation of chondrocytes from calf cartilage. Exp Cell Res 39:59–63

    Article  PubMed  CAS  Google Scholar 

  10. Yasui N, Ochi T, Ono Y (1986) Influence of anti-inflammatory analgesics on metabolism of cartilage. Jpn Pharmacol Ther 14:439–442

    Google Scholar 

  11. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and 15N-nitrate in biological fluids. Anal Biochem 126:131–138

    Article  PubMed  CAS  Google Scholar 

  12. Fukuda K, Ohtani K, Dan H, Tanaka S (1995) Interleukin-1 inhibits keratan sulfate production by rabbit chondrocytes: possible role of prostaglandin E2. Inflamm Res 44:434–437

    Article  PubMed  CAS  Google Scholar 

  13. Abramson SB (1999) The role of COX-2 produced by cartilage in arthritis. Osteoarthr Cartil 7:380–381

    Article  PubMed  CAS  Google Scholar 

  14. Di Battista JA, Dore S, Martel-Pelletier J, Pelletier JP (1996) Prostaglandin E2 stimulates incorporation of proline into collagenase digestible proteins in human articular chondrocytes: identification of an effector autocrine loop involving insulin-like growth factor 1. Mol Cell Endocrinol 123:27–35

    Article  PubMed  CAS  Google Scholar 

  15. Lowe GN, Fu YH, McDougall S, Polendo R, Williams A, Benya PD, Hahn TJ (1996) Effects of prostaglandins on deoxyribonucleic acid and aggrecan synthesis in the RCJ 3.1C5.18 chondrocyte cell line: role of second messengers. Endocrinology 137:2208–2216

    Article  PubMed  CAS  Google Scholar 

  16. Taskiran D, Stefanovic-Racic M, Georgescu H, Evans C (1994) Nitric oxide mediates suppression of cartilage proteogly can synthesis by interleukin-1. Biochem Biophys Res Commun 200:142–148

    Article  PubMed  CAS  Google Scholar 

  17. 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-2 collagen without altering Col2A1 mRNA abundance: prolylhydroxylase as a possible target. Biochem J 324:305–310

    PubMed  CAS  Google Scholar 

  18. Tamura T, Nakanishi T, Kimura Y, Hattori T, Sasaki K, Norimatsu H, Takahashi K, Takigawa M (1996) Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: a possible mechanism of pathological neovascularization in arthritis. Endocrinology 137:3729–3737

    Article  PubMed  CAS  Google Scholar 

  19. Notoya K, Jovanovic D, Reboul P, Johanne M, Mineau F, Pelletier JP (2000) The Induction of cell death in human osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2. J Immunol 165:3402–3410

    PubMed  CAS  Google Scholar 

  20. Fermor B, Weinberg JB, Pisetsky DS, Misukonis MA, Fink C, Guilak F (2002) Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthr Cartil 10:792–798

    Article  PubMed  CAS  Google Scholar 

  21. Pelletier JP, Fernandes JC, Jovanovic DV, Reboul P, Martel-Pelletier J (2001) Chondrocyte death in experimental osteoarthritis is mediated by MEK1/2 and p38 pathways: role of cyclooxygenase-2 and inducible nitric oxide synthase. J Rheumatol 28:2509–2519

    PubMed  CAS  Google Scholar 

  22. Nedelec E, Abid A, Cipolletta C, Presle N, Terlain B, Netter P, Jouzeau J (2001) Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat chondrocyte: lack of contribution to loss of cartilage anabolism. Biochem Pharmacol 61:965–978

    Article  PubMed  CAS  Google Scholar 

  23. Amin AR, Dave M, Attur M, Abramson SB (2000) COX-2, NO, and cartilage damage and repair. Curr Rheumatol Rep 2:447–453

    Article  PubMed  CAS  Google Scholar 

  24. Abramson SB, Attur MG, Amin AR, Clancy R (2001) Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis. Curr Rheumatol Rep 3:535–541

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Although none of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but will be directed solely to a research fund, foundation, educational institution, or other non-profit organization with which one or more of the authors are associated. Medical agents (COX-2 inhibitor, celecoxib) have been supplied by Pfizer. co. Ltd.

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  1. Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, 173-8605, Itabashi-ku, Tokyo, Japan

    Kenta Matsuda, Shigeru Nakamura & Takashi Matsushita

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  1. Kenta Matsuda
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  2. Shigeru Nakamura
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  3. Takashi Matsushita
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Correspondence to Kenta Matsuda.

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Matsuda, K., Nakamura, S. & Matsushita, T. Celecoxib inhibits nitric oxide production in chondrocytes of ligament-damaged osteoarthritic rat joints. Rheumatol Int 26, 991–995 (2006). https://doi.org/10.1007/s00296-006-0107-6

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  • DOI: https://doi.org/10.1007/s00296-006-0107-6

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