Mechanism of mechanical stress in knee osteoarthritis synovial fibrosis mediated via the Piezo1/ERK1/2 axis
10.3969/j.issn.1671-7856.2024.10.006
- VernacularTitle:机械应力经Piezo1/ERK1/2轴介导KOA滑膜纤维化的机制研究
- Author:
Likai YU
1
,
2
;
Di TIAN
;
Zishan SU
;
Lishi JIE
;
Shaobo GUO
;
Peimin WANG
;
Nongshan ZHANG
Author Information
1. 南京中医药大学附属医院/江苏省中医院,南京 210029
2. 南京中医药大学第一临床医学院,南京 210023
- Keywords:
Piezo1;
ERK1/2;
mechanical stress;
KOA synovial fibrosis
- From:
Chinese Journal of Comparative Medicine
2024;34(10):47-56
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Piezo1 activated by mechanical stress on knee osteoarthritis synovial fibrosis via the extracellular signal-regulated kinase(ERK)1/2 signaling pathway.Methods Twenty-five Sprague Dawley rats were divided into blank,exercise,exercise+GsMTx4,exercise+PD98059,and exercise+GsMTx4+PD98059 groups(n=5 per group).After modeling,serum and synovial tissue were extracted and collagen deposition was evaluated by Sirius red and Masson staining.Expression levels of Piezo1,ERK1/2,phospho(p)-ERK1/2,α-smooth muscle actin(SMA),transforming growth factor(TGF)-β,Collagen Ⅰ,and tissue inhibitor of metalloproteinase(TIMP)-1 were detected by Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α contents were detected by enzyme-linked immunosorbent assay.For cell experiments,synovial cells were divided into blank,pull,pull+GsMTx4,pull+PD98059,and pull+GsMTx4+PD98059 groups and the above indices were detected in the model cells by Western blot,RT-qPCR,and other techniques.Results Mechanical stress increased collagen deposition in synovial tissues in the rats,and increased the protein and mRNA expression levels of the pathway-related and fibrosis-specific indicators Piezo1,p-ERK/ERK,α-SMA,TGF-β,Collagen I,and TIMP-1(P＜0.05).Piezo1 expression was significantly down-regulated by both inhibitors(P＜0.05),but the ERK inhibitor(PD98059)had no significant effect on Piezo1 gene expression.Levels of serum inflammatory factors were significantly higher in the exercise group compared with the blank group(P＜0.05),and levels were significantly reduced by the inhibitors(P＜0.05).The in vitro experiments showed the same trends as the animal experiments.Conclusions The Piezo1 ion channel can sense mechanical stress and activate the ERK 1/2 pathway to mediate knee synovial fibrosis.
