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

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.