Chondrocyte autophagy mediated by T-2 toxin via AKT/TSC/Rheb/mTOR signaling pathway and protective effect of CSA-SeNP.

Autor: Lin X; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: linxue1997601@163.com., Liu H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China., Qiao L; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: qlc978402409@163.com., Deng H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: denghuan0205@163.com., Bao M; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: 1193391597@qq.com., Yang Z; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: 1034804083@qq.com., He Y; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: 502917353@qq.com., Xiang R; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: 17323475180@163.com., He H; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China. Electronic address: hf1545767596@163.com., Han J; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: bbbishop@126.com.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2024 Oct; Vol. 32 (10), pp. 1283-1294. Date of Electronic Publication: 2024 May 28.
DOI: 10.1016/j.joca.2024.05.007
Abstrakt: Objective: Kashin-Beck disease (KBD) is an endemic, degenerative, and cartilage-damaging disease for which low selenium and T-2 toxins are considered environmental pathogenic factors. This study aimed to investigate the molecular mechanisms of autophagy in cartilage damage caused by T-2 toxin and the protective effect of chondroitin sulfate A nano-elemental selenium (CSA-SeNP) on the cartilage.
Methods: KBD chondrocytes and C28/I2 human chondrocyte cell lines were used. T-2 toxin, AKT inhibitor, and CSA-SeNP treatment experiments were conducted separately, with a treatment time of 24 h. Autophagy was monitored using MDC staining, and mRFP-GFP-LC3 adenovirus, respectively. RT-qPCR and western blotting were used to detect the expression of the relevant genes and proteins.
Results: The suppression of autophagy observed in KBD chondrocytes was replicated by applying 10 ng/mL T-2 toxin to C28/I2 chondrocytes for 24 h. The AKT/TSCR/Rheb/mTOR signaling pathway was activated by T-2 toxin, which inhibits autophagy. The supplementation with CSA-SeNP alleviated the inhibition of autophagy by T-2 toxin through the AKT/TSCR/Rheb/mTOR signaling pathway.
Conclusions: Loss of autophagy regulated by the AKT/TSCR/Rheb/mTOR signaling pathway plays an important role in cartilage damage caused by T-2 toxin. CSA-SeNP supplementation attenuated inhibition of autophagy in chondrocytes by T-2 toxin by modulating this signaling pathway. These findings provide promising new targets for the prevention and treatment of cartilage disease.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest. The study sponsors were not involved in the study design, data collection, analysis or interpretation, or in the writing of the manuscript. Neither did they affect the decision to submit the manuscript for publication.
(Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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