Department of Respiratory Medicine, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Biomed Pharmacother. 2017 May;89:1262-1268. doi: 10.1016/j.biopha.2017.03.028. Epub 2017 Mar 17.
Endoplasmic reticulum (ER) stress-induced chondrocyte apoptosis plays a critical role in osteoarthritis cartilage degeneration. Previous studies showed that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited chondroprotective activity through inhibiting PGE2-induced ER stress and down regulating the expression of GSK-3β. To further investigate the role of GSK-3β in ER stress-induced chondrocytes apoptosis and the protective role of TMF, GSK-3β siRNA and pcDNA3.1-myc-GSK-3β were employed to knock down and overexpress GSK-3β, respectively, in chondrocytes. Results showed that TM-induced ER stress significantly promoted chondrocytes apoptosis. These could be effectively reversed by GSK-3β deficiency, while GSK-3β overexpression significantly up regulated ER stress and increased chondrocytes apoptosis. In addition, TMF down regulated the expression of GSK-3β and inhibited ER stress-induced chondrocytes apoptosis. Collectively, TMF is a potential natural compound with chondroprotective property through inhibition of ER stress-induced apoptosis with down regulation of GSK-3β.
内质网（ER）应激诱导的软骨细胞凋亡在骨关节炎软骨退变中起关键作用。先前的研究表明，5,7,3',4'-四甲氧基黄酮（TMF）通过抑制 PGE2 诱导的 ER 应激和下调 GSK-3β 的表达表现出软骨保护活性。为了进一步研究 GSK-3β 在 ER 应激诱导的软骨细胞凋亡中的作用以及 TMF 的保护作用，使用 GSK-3β siRNA 和 pcDNA3.1-myc-GSK-3β 分别敲低和过表达 GSK-3β，以在软骨细胞中。结果表明，TM 诱导的 ER 应激显著促进软骨细胞凋亡。GSK-3β 缺乏可有效逆转这种情况，而 GSK-3β 过表达则显著上调 ER 应激并增加软骨细胞凋亡。此外，TMF 下调 GSK-3β 的表达并抑制 ER 应激诱导的软骨细胞凋亡。总之，TMF 是一种潜在的天然化合物，具有通过抑制 GSK-3β 下调抑制 ER 应激诱导的凋亡的软骨保护特性。
