Urinary-derived stem cells protect osteoarthritic chondrocytes by inhibiting the PI3K/AKT pathway
10.3969/j.issn.1000-6710.2024.11.005
- VernacularTitle:尿源干细胞通过抑制PI3K/AKT通路保护骨关节炎软骨细胞
- Author:
Yunan HU
1
;
Lei FAN
1
;
Xiaolong YANG
1
;
Tianhao XU
1
;
Weili FU
1
Author Information
1. 四川大学华西医院运动医学中心(四川成都 610000);四川大学华西医院骨科/骨科研究所(四川成都 610000)
- Publication Type:Journal Article
- Keywords:
urine-derived stem cells;
osteoarthritis;
chondrocytes;
PI3K/AKT/mTOR;
autophagy
- From:
Chinese Journal of Sports Medicine
2024;43(11):885-894
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether the effect of urine-derived stem cells(USCs)on chondro-cytes in osteoarthritis(OA)is related to the PI3K/AKT pathway.Methods Human urine was collected aseptically,and primary USCs were isolated and cultured through specific steps.Meanwhile,chondro-cytes were extracted from the knee joints of Sprague-Dawley rats to establish the OA model.USCs were co-cultured with OA chondrocytes by using Transwell co-culture system,and the transcriptome changes of chondrocytes before and after co-culture were analyzed by using the high-throughput RNA sequencing.Moreover,the phosphorylation levels of key proteins of the PI3K/AKT/mTOR pathway were detected using protein immunoblotting,and the PI3K agonist 740 Y-P was employed to further vali-date the relationship between the protective effect of USCs on OA chondrocytes,as well as its possi-ble relationship to the PI3K/AKT pathway and the possible mechanism.Results Transcriptomic analysis showed that the protective effect of USCs on OA chondrocytes might be related to the'PI3K-Akt sig-naling pathway'.Protein level analysis confirmed that USCs significantly inhibited the PI3K/AKT/mTOR pathway in OA chondrocytes.Moreover,protein immunoblotting and immunofluorescence showed that USCs improved the expression of OA-related proteins and autophagy-related proteins in OA chondro-cytes.What's more,the inhibitory effect of USCs on the PI3K/AKT/mTOR pathway was partially re-versed by using the PI3K agonist 740 Y-P,while the protective and autophagy-promoting effects of USCs on OA chondrocytes were down-regulated.Conclusion This study reveals the potential protective effect of USCs on OA chondrocytes through inhibition of the PI3K/AKT/mTOR signalling pathway and its close correlation with improved autophagy.Therefore,it provides a research basis and theoretical support for the future application of USCs in the treatment of OA.
