The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis

Li Xin Han, Xiao Li Yang, Wen Yan Sun, Zhao Fang Li, Hao Ren, Bao Rong Li, Rong Qiang Zhang, Dan Dan Zhang, Zi Yun Shi, Ji Feng Liu, Jun Ling Cao, Jian Jun Zhang, Yong Min Xiong

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objective: Selenium deficiency is a risk factor for Kashin-Beck Disease (KBD), an endemic osteoarthropathy. Although promoter hypermethylation of glutathione peroxidase 3 (GPX3) (a selenoprotein) has been identified in several cancers, little is known about promoter methylation and expression of GPX3 and their relation to selenium in KBD. The present study was thus conducted to investigate this research question. Methods: Methylation and expressions of GPX3 in whole blood drawn from 288 KBD patients and 362 healthy controls and in chondrocyte cell line were evaluated using methylation-specific PCR and qRT-PCR, respectively. The protein levels of PI3K/Akt/c-fos signaling in the whole blood and chondrocyte cell line were determined with Western blotting. Chondrocytes apoptosis were detected by Hoechst 33342 and Annexin V-FITC/PI staining. Results: GPX3 methylation was increased, GPX3 mRNA was decreased, and protein levels in the PI3K/Akt/c-fos signaling pathway were up-regulated in the whole blood collected from KBD patients as compared with healthy controls. Similar results were obtained for chondrocytes injured by oxidative stress. There was a significant, decreasing trend in GPX3 expression across groups of unmethylation, partial methylation, and complete methylation for GPX3, in sequence. Compared with unmethylation group, protein levels in PI3K/Akt/c-fos pathway were enhanced in partial and complete methylation groups. Treatment of chondrocytes with sodium selenite resulted in reduced methylation and increased expression of GPX3 as well as down-regulated level of PI3K/Akt/c-fos proteins. Conclusions: The methylation and expression of GPX3 and expression of PI3K/Akt/c-fos pathway are altered in KBD and these changes are reversible by selenium supplementation.

Original languageEnglish (US)
Pages (from-to)15-22
Number of pages8
JournalBone
Volume117
DOIs
StatePublished - Dec 2018

Keywords

  • DNA methylation
  • Glutathione peroxidase 3
  • Kashin-Beck disease
  • PI3K/Akt/c-fos signaling pathway
  • Selenium

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Fingerprint Dive into the research topics of 'The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Han, L. X., Yang, X. L., Sun, W. Y., Li, Z. F., Ren, H., Li, B. R., Zhang, R. Q., Zhang, D. D., Shi, Z. Y., Liu, J. F., Cao, J. L., Zhang, J. J., & Xiong, Y. M. (2018). The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis. Bone, 117, 15-22. https://doi.org/10.1016/j.bone.2018.08.017