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

Publication date: Available online 29 January 2020Source: Chemico-Biological InteractionsAuthor(s): Hai Li, Jianhai Chen, Biao Li, Xiaoyan FangAbstractOsteoarthritis (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 ...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research