ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Epigenomics and Epigenetics
Effects of Selenium-mediated RUNX2 Overexpression and its Transcriptome Alterations on Chondrocyte Injury in Kashin Beck disease
Provisionally accepted
- 1Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- 2Xi'an Jiaotong University Health Science Center, Xi'an, China
- 3Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'An, China
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Objective: Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy characterized by excessive apoptosis and matrix destruction. Micronutrient selenium (Se) deficiency is recognized as a major environmental risk factor. This study aimed to investigate the role of RUNX2 in cartilage injury associated with KBD. Methods: RUNX2 expression in articular cartilage from KBD patients was assessed by immunohistochemistry. RUNX2 mRNA expression and promoter methylation were analyzed using qRT-PCR and qMSP. A chondrocyte injury model was established under Se-deficient conditions, while a RUNX2 overexpression model was generated by lentiviral transfection and further analyzed by RNA sequencing. Results: The proportion of RUNX2-positive cells in KBD cartilage was significantly higher than in controls. RUNX2 mRNA levels were elevated, whereas methylation levels were reduced in KBD samples. Inhibition of DNA methylation confirmed that decreased methylation of RUNX2 promoted its transcription. In Se-deficient chondrocytes, decreased RUNX2 methylation, increased RUNX2 expression, and higher rates of apoptosis and necrosis were observed, all of which were reversed by Se supplementation. Moreover, RUNX2 overexpression further increased chondrocyte apoptosis and necrosis. Transcriptomic analysis revealed 263 upregulated and 216 downregulated genes, predominantly enriched in the TNF and MAPK signaling pathways. Conclusions: Micronutrient Se deficiency may contribute to the pathogenesis of KBD by modulating RUNX2 expression and inducing excessive chondrocyte apoptosis, while Se supplementation exerts a protective effect. RUNX2 plays a critical role in KBD progression and may represent a potential therapeutic target.
Keywords: Kashin-Beck Disease, Se deficiency, RUNX2, Chondrocyte injury, RNA transcription profiles
Received: 18 Aug 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Zhang, Li, Yang, Xiong and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yongmin Xiong, xiongym@xjtu.edu.cn
Shiquan Sun, sqsunsph@xjtu.edu.cn
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