Shakibaei Mehdi, John Thilo, Seifarth Claudia, Mobasheri Ali
Institute of Anatomy, Musculoskeletal Research Group, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich.
Ann N Y Acad Sci. 2007 Jan;1095:554-63. doi: 10.1196/annals.1397.060.
Resveratrol is a polyphenolic phytoalexin that is present in various fruits, in the skin of red grapes and peanuts. Recent studies have shown that resveratrol exhibits potent antioxidant properties and is able to exert anti-inflammatory and anti-catabolic properties in several cell types. The pro-inflammatory cytokine interleukin-1beta (IL-1beta) plays a pivotal role in the pathogenesis of osteoarthritis (OA) in humans and animals. In this article we investigated whether resveratrol is able to block the effects of IL-1beta, specifically the activation of caspase-3 and subsequent cleavage of poly (ADP-ribose) polymerase (PARP) in human articular chondrocytes. Cultures of human chondrocytes were prestimulated with 10 ng/mL IL-1beta for 1, 12, and 24 h before being co-treated with IL-1beta and 100 microM resveratrol or 50 microM of the caspase inhibitor Z-DEVD-FMK for 1, 12, and 24 h, respectively in vitro. Resveratrol significantly reduced the IL-1beta-induced inhibition of expression of cartilage-specific collagen type II and signal transduction receptor beta1-integrin in a time-dependent manner. Incubation of chondrocytes with IL-1beta resulted in the activation of caspase-3 and PARP cleavage. These effects were abolished through co-treatment with resveratrol. Furthermore, co-treatment of IL-1beta-stimulated cells with the caspase inhibitor Z-DEVD-FMK blocked activation of caspase-3 and PARP cleavage, suggesting that this process is a caspase-dependent pathway. In summary, our results confirm that resveratrol is an effective inhibitor of chondrocyte apoptosis in vitro. These findings suggest that this dietary polyphenolic compound may have future applications in the nutraceutical-based therapy of human and animal OA.
白藜芦醇是一种多酚类植物抗毒素，存在于各种水果、红葡萄皮和花生中。最近的研究表明，白藜芦醇具有强大的抗氧化特性，并且能够在几种细胞类型中发挥抗炎和抗分解代谢特性。促炎细胞因子白细胞介素-1β（IL-1β）在人类和动物骨关节炎（OA）的发病机制中起关键作用。在本文中，我们研究了白藜芦醇是否能够阻断IL-1β的作用，特别是在人关节软骨细胞中半胱天冬酶-3的激活以及随后聚（ADP-核糖）聚合酶（PARP）的裂解。在体外分别用10 ng/mL IL-1β预刺激人软骨细胞培养物1、12和24小时，然后分别与IL-1β和100 μM白藜芦醇或50 μM半胱天冬酶抑制剂Z-DEVD-FMK共同处理1、12和24小时。白藜芦醇以时间依赖性方式显著降低了IL-1β诱导的软骨特异性II型胶原蛋白表达抑制和信号转导受体β1-整合素的表达。用IL-1β孵育软骨细胞导致半胱天冬酶-3的激活和PARP裂解。通过与白藜芦醇共同处理，这些作用被消除。此外，用半胱天冬酶抑制剂Z-DEVD-FMK共同处理IL-1β刺激的细胞可阻断半胱天冬酶-3的激活和PARP裂解，表明该过程是一条半胱天冬酶依赖性途径。总之，我们的结果证实白藜芦醇在体外是软骨细胞凋亡的有效抑制剂。这些发现表明，这种膳食多酚化合物可能在基于营养保健品的人类和动物OA治疗中有未来应用。
