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Effects of Selenoprotein S Knockdown on Endoplasmic Reticulum Stress in ATDC5 Cells and Gene Expression Profiles in Hypertrophic Chondrocytes

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Abstract

Selenoprotein S (SelS), a member of the selenoprotein family, is mainly located on the endoplasmic reticulum (ER) membrane. SelS is involved in a variety of biological processes, including oxidative stress, inflammation, glucose metabolism regulation, and ER-associated protein degradation (ERAD). This study was designed to explore the role of SelS in chondrocytes. It was confirmed that SelS is a Se-sensitive selenoprotein in low-selenium rat and cell models. ER stress was not induced in SelS knockdown ATDC5 cells. However, treatment of ATDC5 cells with tunicamycin (Tm), an ER stress inducer, increased the expression of SelS, and knockdown of SelS aggravated ER stress induced by Tm, suggesting that SelS is a regulatory molecule involved in ER stress in chondrocytes. Both osteoarthritis and Kashin-Beck disease are osteochondral diseases associated with hypertrophic chondrocyte abnormalities. Therefore, ATDC5 cells were induced to hypertrophic chondrocytes. SelS was knocked down and RNA sequencing was performed. Bioinformatics analysis of the differentially expressed genes (DEGs) revealed that SelS knockdown affected a variety of biological processes, including cell adhesion, osteoclast differentiation, and extracellular matrix homeostasis. Collectively, this study verified that SelS is sensitive to selenium levels and is an ER stress-responsive molecule. Knocking down SelS can cause abnormal expression of adhesion molecules and matrix homeostasis disorder in hypertrophic chondrocytes.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No.81872565).

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  1. Hui Wang and Zhengzheng Li contributed equally to this manuscript.

Authors and Affiliations

  1. Key Laboratory of Environment and Genes Related to Diseases in the Education Ministry and Key Laboratory of Trace Elements and Endemic Diseases in Ministry of Health, School of Public Health, Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Hui Wang, Zhengzheng Li, Yinan Liu, Meng Zhang, Yawen Shi, Ying Zhang, Ge Mi, Mengying Wang, Ying He, Yonghui Chen & Jinghong Chen

  2. School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, 4072, Australia

    Chen Chen

  3. Clinical Research Center for Endemic Disease of Shaanxi Province, Xi’an, Shaanxi, China

    Jinghong Chen

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Wang, H., Li, Z., Liu, Y. et al. Effects of Selenoprotein S Knockdown on Endoplasmic Reticulum Stress in ATDC5 Cells and Gene Expression Profiles in Hypertrophic Chondrocytes. Biol Trace Elem Res 201, 1965–1976 (2023). https://doi.org/10.1007/s12011-022-03313-4

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