Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo.
Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo.
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DOI：
10.1002/art.38133
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发表时间：
2013-12
影响因子：
--
通讯作者：
Clark, Ian M.
中科院分区：
文献类型：
--
作者：
Davidson, Rose K.;Jupp, Orla;de Ferrars, Rachel;Kay, Colin D.;Culley, Kirsty L.;Norton, Rosemary;Driscoll, Clare;Vincent, Tonia L.;Donell, Simon T.;Bao, Yongping;Clark, Ian M.
据报道，萝卜硫素（SFN）可以调节与慢性疾病相关的信号通路。本研究的目的是调查 SFN 治疗对软骨细胞信号通路的影响，并确定萝卜硫素是否可以阻止骨关节炎中的软骨破坏。在体外检查了转录因子 NF-E2 相关因子 2 (Nrf2) 和 NF-κB 的基因表达、组蛋白乙酰化和信号传导。使用牛鼻软骨外植体模型和小鼠骨关节炎的内侧半月板 (DMM) 不稳定模型来评估组织和整体动物水平的软骨保护作用。 SFN 抑制原代人关节软骨细胞和成纤维细胞样滑膜细胞中细胞因子诱导的金属蛋白酶表达。 SFN 独立于 Nrf2 和组蛋白脱乙酰酶活性来调节人关节软骨细胞中的金属蛋白酶表达，但确实介导 JNK 和 p38 MAPK 的延长激活。 SFN 至少通过抑制人关节软骨细胞中的 DNA 结合来减弱 NF-κB 信号传导，并降低多个 NF-κB 依赖性基因的表达。与单独的细胞因子相比，SFN (10 μM) 在蛋白多糖和胶原蛋白分解水平上消除了细胞因子诱导的牛鼻软骨破坏。富含 SFN 的饮食（3 微摩尔/天 SFN 与对照食物相比）降低了小鼠骨关节炎 DMM 模型中的关节炎评分，同时阻断了早期 DMM 诱导的基因表达变化。 SFN 独立于 Nrf2 抑制与骨关节炎有关的关键金属蛋白酶的表达，并在 NF-κB 水平上阻断炎症，以防止体外和体内软骨破坏。
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.
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DOI：
10.1083/jcb.141.6.1291
发表时间：
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期刊：
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影响因子：
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