当前位置： SCI文献检索 > CHEMICO-BIOLOGICAL INTERACTIONS期刊下所有文献 > The protective effects of dulaglutide against advanced glycation end products (AGEs)-induced degradation of type Ⅱ collagen and aggrecan in human SW1353 chondrocytes.

The protective effects of dulaglutide against advanced glycation end products (AGEs)-induced degradation of type Ⅱ collagen and aggrecan in human SW1353 chondrocytes.

Abstract：

:Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, and the risk of developing OA significantly increases with age as well as with concomitant diseases, such as diabetes. Advanced glycation end products (AGEs) accumulate in the body over time and are associated with increased expression of various molecules involved in the pathophysiology of OA. Prostaglandin E2 (PGE2), along with its precursor cyclooxygenase (COX)-2, plays an integral role in the pathogenesis of OA and is highly upregulated in response to AGEs. The most significant event in OA is excessive degradation of the cartilage extracellular matrix, which is composed primarily of type II collagen and aggrecan. In the present study, we investigated the involvement of the receptor for glucagon-like peptide (GLP)-1 in the response of chondrocytes to insult from AGEs using the selective GLP-1 agonist dulaglutide. Firstly, our results indicate that AGEs reduced the expression of the receptor for GLP-1 (GLP-1R) in human SW1353 chondrocytes. Interestingly, we found that treatment with dulaglutide could ameliorate deterioration of the components of the articular extracellular matrix (ECM), such as type II collagen and aggrecan, induced by AGEs through downregulation of matrix metalloproteinase (MMP)-3 and MMP-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. We also found that dulaglutide exerted a potent inhibitory effect against the expression of several proinflammatory cytokines and chemokines closely associated with OA, as well as the production of reactive oxygen species (ROS). Finally, we showed that the effects of dulaglutide were mediated through the nuclear factor kappa-B (NF-κB) pathway. Our findings indicate that dulaglutide displayed a robust protective effect against AGEs-induced damage in chondrocytes, suggesting that it might be a possible therapeutic agent for the treatment of OA.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Li H,Chen J,Li B,Fang X

doi

10.1016/j.cbi.2020.108968

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

108968

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(19)31507-8

journal_volume

322

pub_type

杂志文章

在线工具

The protective effects of dulaglutide against advanced glycation end products (AGEs)-induced degradation of type Ⅱ collagen and aggrecan in human SW1353 chondrocytes.