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Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency–Induced Chondrocyte Apoptosis

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Abstract

Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy related to selenium (Se) deficiency. Se participates in the synthesis of selenoprotein in the form of selenocysteine. In total, 25 selenoproteins, encoded by 25 genes, are currently found in humans; however, the effects of selenoprotein genes on chondrocyte apoptosis, particularly in apoptosis-related genes, remain poorly elucidated. Therefore, in the current study, the expression of selenoprotein genes and apoptosis-related genes were determined by RT-qPCR in patients and chondrocytes and the correlations between them were analyzed using Pearson and Spearman’s rank correlation, and the chondrocyte apoptosis rate was detected by Annexin V-FITC/PI. The results showed that the mRNA levels of 17 selenoprotein genes were downregulated, whereas two genes were upregulated in patients with KBD. The BAX/BCL2 ratio and the mRNA levels of BAX and P53 were increased, but the mRNA levels of BCL2 and NF-κB p65 were decreased in patients with KBD. The mRNA levels of GPX2, GPX3, DIO1, TXNRD1, TXNRD3, and SPS2 were most closely associated with apoptosis-related genes in patients with KBD. Moreover, in the Se deficiency group, the mRNA levels of GPX3, DIO1, and TXNRD1 were downregulated and GPX activity was decreased, but the late apoptosis rate, the mRNA levels of BAX and P53, and the BAX/BCL2 ratio were increased; the opposite trend was observed in the Se supplement group. Collectively, these results indicate that selenoprotein transcription profile is dysregulated in patients with KBD. Furthermore, the expression of GPX3, DIO1, and TXNRD1 genes might be involved in the development of chondrocyte apoptosis by affecting antioxidant capacity.

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Acknowledgements

The authors thank all the volunteers who participated in this study. The authors are also grateful to Wei Yang, Ce Jiang, and Hao Guo for the sample collection and Xiaoxia Dai for sample preparation. The great help of Wenyan Sun who works at the University of Texas was also appreciated in grammatical or spelling modification for confirming correct scientific English.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81773372, 82073494, and 81573104) and the Fundamental Research Funds for the Central Universities (No. xzy022019062).

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Authors and Affiliations

  1. Institute of Endemic Diseases, School of Public Health, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    XiaoLi Yang, ZhaoFang Li, RongQiang Zhang, Di Zhang, YongMin Xiong, Chen Wang, XueNa Yang & Qiang Li

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  1. XiaoLi Yang
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Contributions

XiaoLi Yang: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, validation, visualization, writing original draft, writing review and editing, funding acquisition. ZhaoFang Li: data curation, formal analysis, investigation, methodology, visualization, writing review and editing. RongQiang Zhang: formal analysis, methodology, validation, writing review and editing. Di Zhang: formal analysis, methodology, visualization, writing review and editing. YongMin Xiong: conceptualization, data curation, formal analysis, funding acquisition, investigation, project administration, supervision, validation, visualization, writing review and editing. Chen Wang: formal analysis, visualization, writing review and editing. XueNa Yang: formal analysis, methodology, writing review and editing. Qiang Li: investigation, formal analysis, methodology.

Corresponding author

Correspondence to YongMin Xiong.

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Ethics approval (2017–612) for the study was given by the Biomedical Ethics Committee of Medical Department, Xi’an Jiaotong University.

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Yang, X., Li, Z., Zhang, R. et al. Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency–Induced Chondrocyte Apoptosis. Biol Trace Elem Res 200, 1508–1517 (2022). https://doi.org/10.1007/s12011-021-02772-5

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