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Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Zhixian Xu1, Tie Ke1, Yongfa Zhang1

  • 1Department of Emergency Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian, P.R. China.

Aging
|June 25, 2020
PubMed

Insights

GPR120 activation may treat osteoarthritis by reducing inflammation and preserving cartilage. This study shows GPR120 agonists like GW9508 prevent cartilage component loss and SOX9 reduction in chondrocytes.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Rheumatology

Background:

  • Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degradation.
  • Key cartilage components like type II collagen and aggrecan are reduced in OA due to excessive catabolism.
  • SOX9, a crucial transcription factor for cartilage synthesis, is downregulated in OA.

Purpose of the Study:

  • To investigate the role of G protein-coupled receptor 120 (GPR120) in osteoarthritis.
  • To explore if GPR120 agonists can protect against cartilage degradation by modulating SOX9 expression.
  • To examine the anti-inflammatory effects of GPR120 agonism in chondrocytes.

Main Methods:

  • Utilized ATDC5 chondrocytes treated with interleukin-1β (IL-1β) to model OA conditions.
  • Administered GPR120 agonists GW9508 and TUG891.
  • Assessed the expression of IL-6, IL-8, SOX9, type II collagen, and aggrecan.
  • Investigated the involvement of CREB signaling pathway.

Main Results:

  • GPR120 agonism significantly reduced IL-1β-induced expression of inflammatory markers IL-6 and IL-8.
  • GW9508 and TUG891 treatment prevented the reduction of SOX9 expression caused by IL-1β.
  • These agonists restored the expression of type II collagen and aggrecan.
  • GW9508's effect on SOX9 was mediated through the CREB pathway, confirming GPR120's requirement.

Conclusions:

  • GPR120 activation demonstrates anti-inflammatory properties in chondrocytes.
  • GPR120 agonists can preserve cartilage matrix components by maintaining SOX9 levels.
  • GW9508, acting via CREB, represents a potential therapeutic strategy for halting or preventing cartilage degradation in osteoarthritis.
Keywords:
GPR120GW9508IL-1βcartilage matrixosteoarthritis

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