Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo.
ABSTRACT Objective: Sulforaphane (SFN) has been reported to regulate signalling pathways relevant to chronic diseases. Our study investigated the impact of sulforaphane treatment on signalling pathways in chondrocytes and whether sulforaphane could block cartilage destruction in osteoarthritis. Methods: Gene expression, histone acetylation, transcription factors nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor kappaB (NF-κB) signalling were examined in vitro The bovine nasal cartilage explant model (BNC) and destabilisation of medial meniscus (DMM) murine model of osteoarthritis were used to assess chondroprotection at the tissue and whole animal level. Results: SFN inhibited cytokine-induced metalloproteinase expression in primary human articular chondrocytes (HACs) and in fibroblast-like synovial cells (FLS). SFN acts independently of the Nrf2 transcription factor and histone deacetylase activity in HACs to regulate metalloproteinase expression, but does mediate prolonged activation of Jun kinase (JNK) and p38 MAP kinase. SFN attenuates NF-κB signalling through at least inhibition of DNA binding in HACs with attenuation of expression of several NF-κB dependent genes. SFN abrogates cytokine-induced destruction of bovine nasal cartilage at the level of both proteoglycan and collagen breakdown (10µM compared to cytokines alone). A SFN-rich diet (3µmol daily dose SFN versus control chow) decreases arthritis score in the DMM murine model of osteoarthritis with a concurrent block of early DMM-induced gene expression changes. Conclusion: SFN inhibits the expression of key metalloproteinases implicated in osteoarthritis independently of Nrf2 and blocks inflammation at the level of NF-κB to protect against cartilage destruction in vitro and in vivo. © 2013 American College of Rheumatology.