Sitagliptin ameliorates advanced glycation end-product (AGE)-induced degradation of extracellular matrix in human primary chondrocytes.
Year: 2019
Type: article
Abstract: 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.
Source: PubMed
Authors: Shijun Zhu, Ye Gu, Wei Wang, Jiaxiang Bai, Gaorang Ge, Wenhao Zhang, Qing Wang, Xiaobin Guo, Long Xiao, Yunxia Tao, Fuwen Niu, Zhikui Nie, Dechun Geng, Zhirong Wang
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2980813053