The mechanism of excessive mechanical stress modulates Piezo1-mediated ferroptosis in chondrocytes
- VernacularTitle:过度机械应力调控Piezo1介导成软骨细胞铁死亡的机制探讨
- Author:
Bin WU
1
;
Zhaoxiang LIU
;
Yuehong ZHANG
;
Changyao WANG
Author Information
- Publication Type:Journal Article
- Keywords: osteoarthritis; chondrocytes; stress,mechanical; ferroptosis; Piezo1
- From: Tianjin Medical Journal 2025;53(1):14-18
- CountryChina
- Language:Chinese
- Abstract: Objective To explore the mechanism of excessive mechanical stress regulated ferroptosis induced by Piezo1 channel in mouse chondrocytes.Methods The experiment was performed on mouse ATDC5 chondrocytes.siRNA-Piezo1 interference plasmid and Piezo1 overexpression plasmid were used to transfect chondrocytes,and mechanical stress stimulation was given.The control group,the mechanical stress stimulation group(MS group),the MS+siRNA-Piezo1 group(MS+sh group)and the MS+Piezo1 overexpression group(MS+OV group)were constructed,respectively.The cell viability,Fe2+,ROS levels,the expression of ferroptosis-related proteins SLC7A11 and GPX4,and the expression of Collagen Ⅱ,MMP-13,Aggrecan and p53 proteins were detected in each group.Results Compared with the control group,the cell viability was decreased in the MS group(P＜0.05).Levels of Fe2+,reactive oxygen species(ROS)and malondialdehyde(MDA)were increased(P＜0.05).Levels of reduced glutathione(GSH)and superoxide dismutase(SOD)were decreased(P＜0.05),and the mitochondrial ridge was decreased detected by transmission electron microscopy.Protein levels of SLC7A11,GPX4,Collagen Ⅱ and Aggrecan were decreased(P＜0.05),while protein levels of p53 and MMP-13 were increased(P＜0.05).Compared with the MS group,Fe2+,ROS and MDA levels were decreased in the MS+sh group(P＜0.05),GSH and SOD levels were increased(P＜0.05),and protein levels of SLC7A11,Collagen Ⅱ,GPX4 and Aggrecan were increased(P＜0.05).The protein levels of MMP-13 and p53 were decreased(P＜0.05).Compared with the MS group,cell viability was decreased(P＜0.05),Fe2+,ROS and MDA levels were increased(P＜0.05),GSH and SOD levels were decreased(P＜0.05),and protein levels of SLC7A11,Collagen Ⅱ,GPX4 and Aggrecan were decreased in the MS+OV group(P＜0.05).Levels of MMP-13 and p53 protein were increased(P＜0.05).Conclusion Excessive mechanical stress can induce chondrocyte ferroptosis and promote extracellular matrix degradation via Piezo1 channel protein.
