Liu Shuan, Yang Hongping, Hu Bing, Zhang Mingyong
Department of Orthopaedics, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China.
Exp Ther Med. 2017 Nov;14(5):5057-5062. doi: 10.3892/etm.2017.5165. Epub 2017 Sep 21.
Osteoarthritis (OA) has become a major public health problem with the increased aging population. Previous studies have demonstrated that resveratrol (RES) was able to increase the level of sirtuin 1 (Sirt1) in OA chondrocytes. However, further investigations are required to elucidate the precise molecular mechanism of RES and the potential link between Sirt1 and RES. Therefore, the present study used 30 clinical OA chondrocyte to examine chondrocyte viability, apoptosis rate and the mRNA and protein expression levels of Sirt1 and relevant genes implicated in apoptosis, extracellular matrix (ECM) degradation and Wnt/β-catenin signaling pathway. RES and nicotinamide were used as the stimulus and inhibitor, respectively. The results demonstrated that the apoptotic rate reduced as the cell population decreased from 13.83 to 6.55% in response to 10 µM RES. Expression levels of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax), procaspase-3 and -9, matrix metalloproteinase 1 (MMP1), MMP3, MMP13, Wnt3a, Wnt5a, Wnt7a and β-catenin were significantly inhibited (P<0.01), whereas the level of Bcl-2 was significantly increased (P<0.01) in OA chondrocytes treated with 10 µM RES. These observations suggested that Sirt1 may regulate apoptosis and ECM degradation in RES-treated osteoarthritis chondrocytes via the Wnt/β-catenin signaling pathway.
随着人口老龄化加剧，骨关节炎（OA）已成为一个主要的公共卫生问题。先前的研究表明，白藜芦醇（RES）能够提高OA软骨细胞中沉默调节蛋白1（Sirt1）的水平。然而，需要进一步研究以阐明RES的确切分子机制以及Sirt1与RES之间的潜在联系。因此，本研究使用30个临床OA软骨细胞来检测软骨细胞活力、凋亡率以及Sirt1和与凋亡、细胞外基质（ECM）降解及Wnt/β-连环蛋白信号通路相关基因的mRNA和蛋白表达水平。分别使用RES和烟酰胺作为刺激物和抑制剂。结果表明，响应10 µM RES，随着细胞数量减少，凋亡率从13.83%降至6.55%。在经10 µM RES处理的OA软骨细胞中，B细胞淋巴瘤2（Bcl-2）相关X蛋白（Bax）、半胱天冬酶原-3和-9、基质金属蛋白酶1（MMP1）、MMP3、MMP13、Wnt3a、Wnt5a、Wnt7a和β-连环蛋白的表达水平受到显著抑制（P<0.01），而Bcl-2水平显著升高（P<0.01）。这些观察结果表明，Sirt1可能通过Wnt/β-连环蛋白信号通路调节RES处理的骨关节炎软骨细胞中的凋亡和ECM降解。
