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首页> 外文期刊>Journal of Cellular Physiology >Biological effects of the plant-derived polyphenol resveratrol in human articular cartilage and chondrosarcoma cells
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Biological effects of the plant-derived polyphenol resveratrol in human articular cartilage and chondrosarcoma cells

机译：植物多酚的生物效应白藜芦醇在人体关节软骨和软骨肉瘤细胞

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The natural phytoestrogen resveratrol (RSV) may have therapeutic potential for arthritic conditions. RSV is chondroprotective for articular cartilage in rabbit models for arthritis, but its biological effects on human articular cartilage and chondrosarcoma cells are unknown. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS4, and ADAMTS5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly also enhances BMP7-promoted proteoglycan synthesis as assessed by 35S-sulfate incorporation. Protein-DNA interaction arrays suggest that RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. We propose that RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma. Our findings suggest that RSV has potential as a unique biologic treatment for both prevention and treatment of cartilage degenerative diseases. J. Cell. Physiol. 227: 3488-3497, 2012.
机译：白藜芦醇的天然植物雌激素(RSV)治疗关节炎的潜力吗条件。关节软骨在兔模型关节炎,但其生物对人类的影响关节软骨和软骨肉瘤细胞未知的。软骨内稳态评估进行了研究生产基质降解酶(MMP-13ADAMTS4 ADAMTS5),以及蛋白多糖生产和合成。RSV反对异化的因素(例如,FGF-2或il - 1β)被体外研究和体外使用单层、三维海藻酸珠子分别和软骨移植组织文化。RSV提高细胞生存能力的关节软骨细胞,有效对抗那是cartilage-degrading蛋白酶生产由分解和/或anti-anabolic细胞因子在人体关节软骨细胞。也大大增强了BMP7-promoted评估35 s-sulfate蛋白合成合并。表明RSV抑制激活的转录因子参与炎症和软骨分解代谢的信号通路,包括直接下游MAPK的监管机构(e.g . AP-1 PEA3)和5κB .妥协人类软骨肉瘤的生存细胞,但不是主要的关节软骨细胞,揭示特异性RSV的活动非致瘤性和tumor-derived细胞。建议RSV chondroprotective程度的发挥部分功能由p53诱导才会安静下来在人类原发性软骨细胞凋亡,但不是人类软骨肉瘤。RSV有潜力作为一种独特的生物治疗为预防和治疗软骨退化性疾病。3488-3497, 2012.

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