Effects of exosomes secreted from mesenchymal stem cells on chondrocyte injury under hypoxia
10.3969/j.issn.1006-5725.2025.22.009
- VernacularTitle:缺氧下间充质干细胞分泌的外泌体对软骨细胞损伤的影响
- Author:
Shaochu CHEN
1
;
Ming GONG
;
Wang ZHANG
;
Jiawen WU
;
Guangxin HUANG
;
Yadong ZHANG
Author Information
1. 南方医科大学第三附属医院骨科医学中心脊柱外科一科(广东 广州 510630);深圳市龙华区人民医院脊柱外科(广东 深圳 518109)
- Publication Type:Journal Article
- Keywords:
osteoarthritis;
cartilage defect;
chondrocyte;
exosome;
ferroptosis
- From:
The Journal of Practical Medicine
2025;41(22):3529-3536
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.
