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 Jiaotong University, Xi'an, Shaanxi 712000, 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.
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 Jiaotong University, Xi'an, Shaanxi 712000, 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.
Ecotoxicol Environ Saf. 2024 Jul 1;279:116503. doi: 10.1016/j.ecoenv.2024.116503. Epub 2024 May 28.
Kashin-Beck disease (KBD) is an endemic, environmentally associated cartilage disease. Previous studies have shown that the environmental suspected pathogenic factors of KBD, T-2 toxin and low selenium, are involved in the regulation of inflammation, oxidative stress and autophagy in some tissues and organs. In cartilage diseases, the level of cellular autophagy determines the fate of the chondrocytes. However, whether autophagy is involved in KBD cartilage lesions, and the role of low selenium and T-2 toxins in KBD cartilage injury and autophagy are still unclear. This work took the classical AMPK/mTOR/ULK1 autophagy regulatory pathway as the entry point to clarify the relationship between the environmental suspected pathogenic factors and chondrocyte autophagy. Transmission electron microscopy was used to observe the autophagy of chondrocytes in KBD patients. qRT-PCR and western blot were used to analyze the expression of AMPK/mTOR/ULK1 pathway and autophagy markers. The rat model of KBD was established by low selenium and T-2 toxin, the autophagy in rat cartilage was detected after 4- and 12-week interventions. Chondrocyte autophagy was found in KBD, and the AMPK/mTOR/ULK1 pathway was down-regulated. In the rat model, the pathway showed an up-regulated trend when low selenium and T-2 toxin, were treated for a short time or low concentration, and autophagy level increased. However, when low selenium and T-2 toxin were treated for a long time or at high concentrations, the pathway showed a down-regulated trend, and the autophagy level was reduced and even defective. In conclusion, in the process of KBD cartilage lesion, chondrocyte autophagy level may increase in the early stage, and decrease in the late stage with the progression of lesion. Low selenium and T-2 toxins may affect autophagy by AMPK/mTOR/ULK1 pathway.
大骨节病（KBD）是一种地方性、环境相关的软骨病。先前的研究表明，KBD 的环境可疑致病因素 T-2 毒素和低硒，参与了一些组织和器官的炎症、氧化应激和自噬的调节。在软骨疾病中，细胞自噬水平决定了软骨细胞的命运。然而，自噬是否参与 KBD 软骨病变，以及低硒和 T-2 毒素在 KBD 软骨损伤和自噬中的作用尚不清楚。本工作以经典的 AMPK/mTOR/ULK1 自噬调控通路为切入点，阐明环境可疑致病因素与软骨细胞自噬的关系。利用透射电镜观察 KBD 患者软骨细胞的自噬情况。qRT-PCR 和 Western blot 分析 AMPK/mTOR/ULK1 通路和自噬标志物的表达。采用低硒和 T-2 毒素建立 KBD 大鼠模型，干预 4 周和 12 周后检测大鼠软骨中的自噬情况。发现 KBD 存在软骨细胞自噬，且 AMPK/mTOR/ULK1 通路下调。在大鼠模型中，低硒和 T-2 毒素短期、低浓度处理时，通路呈上调趋势，自噬水平增加；而长期、高浓度处理时，通路呈下调趋势，自噬水平降低甚至出现缺陷。综上，在 KBD 软骨病变过程中，软骨细胞自噬水平可能在病变早期增加，随着病变进展而减少。低硒和 T-2 毒素可能通过 AMPK/mTOR/ULK1 通路影响自噬。
