Vildagliptin reduced extracellular matrix degradation in human primary chondrocytes

Abstract 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).