The expression of SOCS1 is regulated by promoter DNA methylation and is associated with mitochondria-mediated apoptosis of T-2 induced chondrocytes

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-07-04 DOI:10.1016/j.yexcr.2024.114152

Pengzhen Lei , Xiaoqing Wang , Xiaodong Qu , Rui Qi , Duanmingyu Chen , Yanhai Chang

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Abstract

At present, the function of SOCS1 in Kashin-Beck disease (KBD) has not been reported. This study aims to explore the expression and mechanism of SOCS1 in KBD, and provide theoretical basis for the prevention and treatment of KBD. The expression of SOCS1 were measured by qRT-PCR and Western blot. ELISA was used to detect the content of SOCS1 in serum and synovial fluid. CCK-8 kits were selected to measure the cell viability. Methylation Specific PCR (MSP) assay is used to detect the methylation level of SOCS1 in chondrocytes. Flow cytometry was used to analyze the apoptosis rate of chondrocytes in different groups. The expression of apoptosis related proteins (caspase-3 and caspase-9) and Cytochrome c were detected using Western blot. The mitochondrial ROS, ATP and the activity of mitochondrial respiratory chain complexes were detected using commercial kits. The results showed that the expression of SOCS1 significantly increases in KBD patients and T-2 induced chondrocytes. Further research has found that the methylation levels of SOCS1 were significantly reduced in KBD patients and T-2 induced chondrocytes. Functional studies have found that SOCS1 silencing inhibited chondrocyte apoptosis and mitochondrial dysfunction. More importantly, SOCS1 regulated mitochondrial mediated chondrocyte apoptosis through the IGF-1/IGF-1R/FAK/Drp1 pathway. In conclusion, SOCS1 expression is increased and methylation levels are decreased in KBD, and is involved in regulating mitochondrial mediated apoptosis in T-2 induced chondrocytes through IGF-1/IGF-1R/FAK/Drp1 signaling. This study provides new theoretical basis for the treatment and prevention of KBD in clinical practice.

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SOCS1 的表达受启动子 DNA 甲基化的调控，与线粒体介导的 T-2 诱导的软骨细胞凋亡有关。

目前，SOCS1在卡欣贝克病（KBD）中的功能尚未见报道。本研究旨在探讨SOCS1在KBD中的表达及作用机制，为KBD的预防和治疗提供理论依据。研究采用 qRT-PCR 和 Western blot 检测 SOCS1 的表达。用 ELISA 检测血清和滑液中 SOCS1 的含量。选用 CCK-8 试剂盒检测细胞活力。甲基化特异性 PCR（MSP）检测法用于检测软骨细胞中 SOCS1 的甲基化水平。流式细胞术用于分析不同组软骨细胞的凋亡率。采用 Western 印迹法检测凋亡相关蛋白（caspase-3 和 caspase-9）和细胞色素 c 的表达。使用商业试剂盒检测线粒体 ROS、ATP 和线粒体呼吸链复合物的活性。结果显示，在 KBD 患者和 T-2 诱导的软骨细胞中，SOCS1 的表达明显增加。进一步研究发现，在 KBD 患者和 T-2 诱导的软骨细胞中，SOCS1 的甲基化水平明显降低。功能研究发现，沉默 SOCS1 可抑制软骨细胞凋亡和线粒体功能障碍。更重要的是，SOCS1 通过 IGF-1/IGF-1R/FAK/Drp1 通路调控线粒体介导的软骨细胞凋亡。总之，SOCS1在KBD中表达增加，甲基化水平降低，并通过IGF-1/IGF-1R/FAK/Drp1信号传导参与调控T-2诱导的软骨细胞线粒体介导的凋亡。这项研究为临床治疗和预防KBD提供了新的理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567