The protective effects of exenatide against AGEs-induced articular matrix degradation in human primary chondrocytes.

Osteoarthritis (OA) presents a major global health burden and is projected to become even more prevalent in coming decades. Therefore, it is of utmost importance to uncover novel therapies for the treatment and prevention of this disease. In the present study, we investigated the effects of exenatide, a specific glucagon-like peptide (GLP) agonist, on degradation of type II collagen and aggrecan, the two main components of the articular extracellular matrix, in human primary chondrocytes. Our results reveal that exenatide could ameliorate degradation of type II collagen and aggrecan by inhibiting expression of metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) induced by advanced glycation end-products. We also found that exenatide reduces oxidative stress and inhibits activation of nuclear factor-κB through the p38 cellular signaling pathway. Taken together, the findings of this study indicate that exenatide may have potential as a novel treatment for osteoarthritis.