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Celecoxib inhibits production of MMP and NO via down-regulation of NF-κB and JNK in a PGE2 independent manner in human articular chondrocytes

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Abstract

The purpose of this study was to examine the effects of celecoxib on matrix metalloproteinases (MMP-1 and MMP-3), nitric oxide (NO), and the phosphorylation of nuclear factor-κB (NF-κB) and three mitogen-activated protein kinases (MAPKs), (p38, JNK and ERK) in human articular chondrocytes from normal, osteoarthritis, and rheumatoid arthritis cartilages. Celecoxib at 100 nM reduced the IL-1β-induced productions of MMP-1, MMP-3, iNOS, and NO, whereas indomethacin at 100 nM showed no effect. The additional stimulation of prostaglandin E2 (PGE2) failed to restore those productions, while the production of PGE2 were reduced by 1 and 10 μM but not 100 nM of celecoxib. The inhibitors of NF-κB, JNK and p38, but not ERK, decreased IL-1β-enhanced MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated the phosphorylation of NF-κB and JNK but has no effect on either p38 or ERK. Celecoxib has inhibitory effects on MMP-1, MMP-3 and NO productions, suggesting the protective roles directly on articular chondrocytes. Despite the COX-2 selectivity, celecoxib affects those productions via not PGE2 but NF-κB and JNK MAPK.

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Acknowledgments

The authors thank Drs. Tomoki Aoyama and Hiroyuki Yoshitomi for their valuable helps and thoughtful discussions. The authors also thank Drs. Yasuaki Nakagawa and Masahiko Kobayashi for helping the cartilage retrieval.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo, 606-8507, Kyoto, Japan

    R. Tsutsumi, H. Ito, T. Hiramitsu, K. Nishitani, M. Akiyoshi, T. Kitaori & T. Nakamura

  2. Department of Sports Medicine, Faculty of Sports, Budo, and Health, Tenri University, 80 Taisyo-cho, Tenri, Nara, Japan

    T. Yasuda

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  1. R. Tsutsumi
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  2. H. Ito
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  3. T. Hiramitsu
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Correspondence to H. Ito.

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Tsutsumi, R., Ito, H., Hiramitsu, T. et al. Celecoxib inhibits production of MMP and NO via down-regulation of NF-κB and JNK in a PGE2 independent manner in human articular chondrocytes. Rheumatol Int 28, 727–736 (2008). https://doi.org/10.1007/s00296-007-0511-6

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  • DOI: https://doi.org/10.1007/s00296-007-0511-6

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