Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo
Davidson RK, Jupp O, de Ferrars R, Kay CD, Culley KL, Norton R, Driscoll C, Vincent TL, Donell ST, Bao Y, Clark IM
Arthritis and rheumatism · 71 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Dunhill Medical Trust
- University or hospital
- University of East Anglia
- Nonprofit
- Versus Arthritis
- Government
- Directorate for Biological Sciences
- Government
- Biotechnology and Biological Sciences Research Council
- Grants
- Versus Arthritis (19371); Biotechnology and Biological Sciences Research Council (BB/I006060/1); Biotechnology and Biological Sciences Research Council (BB/I006060/1); Versus Arthritis (20246)
Based on 5 listed funder(s).
Publication
- Published
- 2013-08-27 · Arthritis Rheum · vol. 65 · issue 12 · pp. 3130–3140
- Publisher
- Wiley
- Cited
- 84 citations · more than 94% of similar papers · 4.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 54 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Osteoarthritis Treatment and Mechanisms · Genomics, phytochemicals, and oxidative stress · Rheumatoid Arthritis Research and Therapies
- Keywords
- Sulforaphane, Cartilage, Matrix metalloproteinase, Cell biology, Chemistry, Osteoarthritis, Cancer research, Molecular biology, Biology, Medicine, Pathology, Anatomy, Biochemistry
- MeSH
- cartilage, articular, chondrocytes, animals, cattle, humans, mice, arthritis, experimental, osteoarthritis, isothiocyanates, sulfoxides, matrix metalloproteinases, nf-kappa b, signal transduction, nf-e2-related factor 2
11 authors
From GB
- Rose K. DavidsonUniversity of East Anglia
- Orla J. JuppUniversity of East Anglia
- Rachel de FerrarsUniversity of East Anglia
- Colin D. KayUniversity of East Anglia
- Kirsty L. CulleyUniversity of East Anglia
- Rosemary NortonUniversity of East Anglia
Abstract
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 μM) 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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