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Phase 2 enzyme inducer sulphoraphane blocks matrix metalloproteinase production in articular chondrocytes.
Rheumatology (Oxford). 2009 Aug; 48(8):932-8.R

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-kappaB 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-kappaB 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.

Authors+Show Affiliations

Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Dongan-Gu, Anyang, Korea. kimha@hallym.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19491303

Citation

Kim, Hyun Ah, et al. "Phase 2 Enzyme Inducer Sulphoraphane Blocks Matrix Metalloproteinase Production in Articular Chondrocytes." Rheumatology (Oxford, England), vol. 48, no. 8, 2009, pp. 932-8.
Kim HA, Yeo Y, Kim WU, et al. Phase 2 enzyme inducer sulphoraphane blocks matrix metalloproteinase production in articular chondrocytes. Rheumatology (Oxford). 2009;48(8):932-8.
Kim, H. A., Yeo, Y., Kim, W. U., & Kim, S. (2009). Phase 2 enzyme inducer sulphoraphane blocks matrix metalloproteinase production in articular chondrocytes. Rheumatology (Oxford, England), 48(8), 932-8. https://doi.org/10.1093/rheumatology/kep132
Kim HA, et al. Phase 2 Enzyme Inducer Sulphoraphane Blocks Matrix Metalloproteinase Production in Articular Chondrocytes. Rheumatology (Oxford). 2009;48(8):932-8. PubMed PMID: 19491303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase 2 enzyme inducer sulphoraphane blocks matrix metalloproteinase production in articular chondrocytes. AU - Kim,Hyun Ah, AU - Yeo,Yunshin, AU - Kim,Wan-Uk, AU - Kim,Suho, Y1 - 2009/06/02/ PY - 2009/6/4/entrez PY - 2009/6/6/pubmed PY - 2009/9/11/medline SP - 932 EP - 8 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 48 IS - 8 N2 - 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-kappaB 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-kappaB 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. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/19491303/Phase_2_enzyme_inducer_sulphoraphane_blocks_matrix_metalloproteinase_production_in_articular_chondrocytes_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kep132 DB - PRIME DP - Unbound Medicine ER -