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Rheumatology Advance Access published online on June 2, 2009
Rheumatology, doi:10.1093/rheumatology/kep132
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Phase 2 enzyme inducer sulphoraphane blocks matrix metalloproteinase production in articular chondrocytes

Hyun Ah Kim1, Yunshin Yeo1, Wan-Uk Kim2 and Suho Kim1

1Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang and 2Department of internal medicine, Catholic University, Seoul, Korea.

Correspondence to: Hyun Ah Kim, Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 896, Pyongchondong, Dongan-gu, Anyang, Kyunggi-do, 431-070, Korea. E-mail: kimha{at}hallym.ac.kr


  Abstract

Objectives. In addition to its chemopreventive activity, phase 2 enzyme inducers have been recently found to have anti-inflammatory activity. In this study, we examined the influence of sulphoraphane (SPN), one of the most potent inducers of the phase II enzymes on the production of MMPs by pro-inflammatory cytokines in human articular chondrocytes.

Methods. Articular cartilages were obtained from knee OA patients and were cultured in monolayers and explants. Induction of a phase II enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), in chondrocytes was assayed after incubation with various concentrations of SPN. Chondrocytes were stimulated with IL-1 or TNF-{alpha} with or without pre-incubation with SPN. The expression and activation of MMP-1, -3 and -13 was evaluated by an ELISA, gel zymography and RT–PCR. MAP kinases [p38, extracellular signal-regulated protein kinase (ERK) and C-Jun N terminal kinase (JNK)] and NF-{kappa}B activation were evaluated by western blotting and by an electrophoretic mobility shift assay, respectively.

Results. SPN significantly induced NQO1 activity in chondrocytes and the induction was maximal at 24 h. SPN inhibited the production of MMP-1, -3 and -13 protein and mRNA induced by either IL-1 or TNF-{alpha} in a dose-dependent manner. This inhibition of MMP by SPN was accompanied by the inhibition of NF-{kappa}B and JNK activation.

Conclusions. SPN was found to inhibit MMP production in pro-inflammatory cytokine-stimulated chondrocytes. Delineation of the biochemical mechanism regulating cartilage catabolism by SPN may identify safe and effective therapeutic targets for the inhibition of cartilage degradation.

KEY WORDS: Chondrocyte, Phase 2 enzymes, Sulphoraphane, MMP, IL-1, TNF-{alpha}

Submitted 4 June 2008; revised version accepted 22 April 2009. Accepted 22 April 2009


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