Department of Orthopedics, Zhangjiagang Hospital of Traditional Chinese Medicine, China.
Orthopedics and Sports Medicine Center, Suzhou Municipal Hospital (North District), Nanjing Medical University Affiliated Suzhou Hospital, 242, Guangji Road, Suzhou 215006, China.
Eur J Pharmacol. 2019 Feb 5;844:49-55. doi: 10.1016/j.ejphar.2018.11.020. Epub 2018 Nov 16.
In the present study, we investigated the effects of the specific DPP-4 inhibitor vildagliptin on degradation of type II collagen and aggrecan, the main components of the articular extracellular matrix, in primary human chondrocytes. The results of our study reveal that vildagliptin reduced degradation of the articular extracellular matrix (ECM) by downregulating IL-1β-induced expression of matrix metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5). We also found that vildagliptin ameliorated IL-1β-induced activation of the JNK/AP-1 and nuclear factor-κB (NF-κB) pro-inflammatory signaling pathways by downregulating phosphorylation of JNK and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα), activation of c-Fos/c-Jun, and nuclear translocation of p65. Our findings suggest that vildagliptin may serve as a novel treatment for excessive degradation of the articular ECM in osteoarthritis (OA).
在本研究中，我们研究了特异性 DPP-4 抑制剂维格列汀对人原代软骨细胞中 II 型胶原和聚集蛋白聚糖（关节细胞外基质的主要成分）降解的影响。我们的研究结果表明，维格列汀通过下调 IL-1β 诱导的基质金属蛋白酶-3（MMP-3）、基质金属蛋白酶-13（MMP-13）、解整合素金属蛋白酶与凝血酶敏感蛋白-4（ADAMTS-4）和解整合素金属蛋白酶与凝血酶敏感蛋白-5（ADAMTS-5）的表达，减少了关节细胞外基质（ECM）的降解。我们还发现，维格列汀通过下调 JNK 和核因子κB（NF-κB）炎症信号通路中 JNK 的磷酸化和κ轻链增强子核因子 B 抑制物α（IκBα）的激活、c-Fos/c-Jun 的激活以及 p65 的核转位，改善了 IL-1β 诱导的 JNK/AP-1 和 NF-κB 炎症信号通路的激活。我们的研究结果表明，维格列汀可能成为治疗骨关节炎（OA）关节 ECM 过度降解的一种新方法。
