Open AccessSulforaphane Represses Matrix‐Degrading Proteases and Protects Cartilage From Destruction In Vitro and In Vivo
Author(s) -
Davidson Rose K.,
Jupp Orla,
Ferrars Rachel,
Kay Colin D.,
Culley Kirsty L.,
Norton Rosemary,
Driscoll Clare,
Vincent Tonia L.,
Donell Simon T.,
Bao Yongping,
Clark Ian M.
Publication year - 2013
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.38133
Subject(s) - sulforaphane , cartilage , matrix metalloproteinase , chemistry , microbiology and biotechnology , osteoarthritis , histone deacetylase , inflammation , cancer research , immunology , histone , medicine , biology , pathology , biochemistry , anatomy , gene , alternative medicine
Objective Sulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis. Methods Gene expression, histone acetylation, and signaling of the transcription factors NF‐E2–related factor 2 (Nrf2) and NF‐κB were examined in vitro. The bovine nasal cartilage explant model and the destabilization of the medial meniscus (DMM) model of osteoarthritis in the mouse were used to assess chondroprotection at the tissue and whole‐animal levels. Results SFN inhibited cytokine‐induced metalloproteinase expression in primary human articular chondrocytes and in fibroblast‐like synovial cells. SFN acted independently of Nrf2 and histone deacetylase activity to regulate metalloproteinase expression in human articular chondrocytes but did mediate prolonged activation of JNK and p38 MAPK. SFN attenuated NF‐κB signaling at least through inhibition of DNA binding in human articular chondrocytes, with decreased expression of several NF‐κB–dependent genes. Compared with cytokines alone, SFN (10 μ M ) abrogated cytokine‐induced destruction of bovine nasal cartilage at both the proteoglycan and collagen breakdown levels. An SFN‐rich diet (3 μmoles/day SFN versus control chow) decreased the arthritis score in the DMM model of osteoarthritis in the mouse, 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.