Downregulated Expression and Hypermethylation of SIRT1 in Patients with Kashin-Beck Disease-Mediated Chondrocyte Apoptosis May Potentially Be Ameliorated by Selenium Supplement

• Published in: Biological trace element research
• Main Authors: Yang, Xiaoli, Han, Lixin, Zhang, Di, Xu, Cuixiang, Jin, Zhankui, Xiong, Yongmin
• Format: Journal Article
• Language: English
• Published: United States 23-09-2024
• Subjects: DNA methylation; T-2 toxin; Se deficiency; SIRT1; Kashin-Beck disease; Apoptosis
• ISSN: 0163-4984; 1559-0720; 1559-0720
• DOI: 10.1007/s12011-024-04362-7

This study aims to elucidate the role of silent information regulator 2 homologue 1 (SIRT1) in cartilage damage in Kashin-Beck disease (KBD) by exploring the correlation between SIRT1 and KBD and the potential effect of SIRT1 expression and methylation on chondrocyte apoptosis. SIRT1 protein expression was detected using IHC, and the mRNA levels of SIRT1, DNMTs, and apoptosis-related genes were measured by RT-qPCR. Methylation levels of SxIRT1 were detected by MALDI-TOF-MS, MSP, and qMSP. Chondrocyte apoptosis was determined by Hoechst 33,342 staining and Annexin V-FITC/PI following selenium (Se) deficiency or T-2 toxin and Se supplement. Both protein and mRNA levels of SIRT1 were reduced in KBD patients, and SIRT1 expression discriminated between KBD and non-KBD with an AUC greater than 0.7. Methylation levels of SIRT1 were significantly elevated in KBD patients, and SIRT1 hypermethylation increased the risk of acquiring KBD 3.879-fold. DNMTs mRNA levels were increased in KBD patients, and further, DNMT1 mRNA levels were decreased, and SIRT1 mRNA levels were increased in the SIRT1 hypomethylation group. Moreover, the SIRT1 expression was negatively correlated with pro-apoptotic genes and positively correlated with anti-apoptotic gene expression, especially in KBD patients. Furthermore, apoptosis rates, DNMT1 mRNA level, and SIRT1 methylation level were increased in chondrocytes treated with Se deficiency and T-2 toxin, but SIRT1 mRNA level was downregulated, whereas the opposite trend was observed in chondrocytes treated with Se supplement. Low SIRT1 expression and CpG hypermethylation in KBD patients are associated with increased disease risk, which mediated chondrocyte apoptosis can be ameliorated by Se supplement.