Sitagliptin ameliorates advanced glycation end-product (AGE)-induced degradation of extracellular matrix in human primary chondrocytes

American Journal of Translational Research

Jiaxiang Bai¹  Wei Wang²  Ye Gu³  Shijun Zhu⁴ 

[1] Department of Orthopaedics, Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou 215600, China;Department of Orthopedics, Changshu Hospital Affiliated to Soochow University, First Peoples Hospital of Changshu City, Changshu 215500, China;Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, China;Department of Ortopaedics, Affiliated Jining NO.1 Peoples Hospital of Jining Medical University, Jining Medical University, Jining 272011, China

关键词: Osteoarthritis (OA);    sitagliptin;    dipeptidyl peptidase IV (DPP-4);    advanced glycation end-products (AGEs);    matrix metalloproteinases (MMPs);    a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS);   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Accumulation of advanced glycation end-products (AGEs) increases inflammation and triggers processes involved in the pathogenesis of osteoarthritis (OA). As a major debilitating age-related disease, it is imperative that novel therapies for OA be sought. In the present study, we investigated the effects of the selective dipeptidyl peptidase IV (DPP-4) inhibitor sitagliptin in human primary chondrocytes exposed to insult by AGEs to elucidate the potential role of sitagliptin in the treatment of OA. Our findings show that inhibition of DPP-4 by sitagliptin could reduce oxidative stress, increase cell viability and prevent degradation of type II collagen and aggrecan by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) induced by AGEs in human primary chondrocytes. Mechanistically, we found that sitagliptin inhibited AGEs-induced nuclear translocation of p65 protein and drastically decreased the luciferase activity of NF-κB. These findings indicate that sitagliptin may have potential as a novel therapeutic option for the treatment and prevention of OA.

【 授权许可】

CC BY-NC