Drs. Davidson and Jupp contributed equally to this work.
Sulforaphane Represses Matrix-Degrading Proteases and Protects Cartilage From Destruction In Vitro and In Vivo
Version of Record online: 27 NOV 2013
© The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Arthritis & Rheumatism
Volume 65, Issue 12, pages 3130–3140, December 2013
How to Cite
Davidson, R. K., Jupp, O., de Ferrars, R., Kay, C. D., Culley, K. L., Norton, R., Driscoll, C., Vincent, T. L., Donell, S. T., Bao, Y. and Clark, I. M. (2013), Sulforaphane Represses Matrix-Degrading Proteases and Protects Cartilage From Destruction In Vitro and In Vivo. Arthritis & Rheumatism, 65: 3130–3140. doi: 10.1002/art.38133
- Issue online: 27 NOV 2013
- Version of Record online: 27 NOV 2013
- Accepted manuscript online: 27 AUG 2013 03:31PM EST
- Manuscript Accepted: 8 AUG 2013
- Manuscript Received: 18 OCT 2012
- Biotechnology and Biological Sciences Research Council (Diet and Health Research Industry Club). Grant Number: BB/I006060/1
- Dunhill Medical Trust. Grant Number: R73/0208
- Arthritis Research UK. Grant Number: 19371
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.
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.
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.
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.