Research Paper Volume 12, Issue 12 pp 12074—12085
Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9
- 1 Department of Emergency Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian, P.R. China
Received: November 21, 2019 Accepted: April 7, 2020 Published: June 24, 2020https://doi.org/10.18632/aging.103375
How to Cite
Copyright © 2020 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Osteoarthritis (OA) is a whole-joint disease with extremely high prevalence. In all treatment approaches of OA, blocking the degradation of the cartilage extracellular matrix is an important treatment. In OA, overexpression of derivative enzymes leads to excessive catabolism and reduced synthesis of cartilage including type II collagen and aggrecan, which results in irreversible destruction of the joint. SOX9 is a transcription factor that regulates the synthesis of type II collagen and aggrecan and is significantly downregulated in OA. GPR120 has been reported to affect the pathophysiology of OA. In this study, we used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1β to investigate the involvement of GPR120 in SOX9-mediated expression of type II collagen and aggrecan. Our findings show that agonism of GPR120 can reduce inflammation by inhibiting the expression of IL-6 and IL-8 induced by IL-1β. We also show that GW9508 and TUG891 rescue the expression of type II collagen and aggrecan by preventing the reduction of SOX9 expression. Additionally, we demonstrate that the effects of GW9508 on SOX9 expression are mediated through CREB and that GPR120 is indeed required for this effect. Thus, agonism of GPR120 by GW9508 might be a potential therapeutic strategy to halt or prevent cartilage degradation.