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, Jianjun Zhang , Yong Min Xiong

Research output: Contribution to journalArticle

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 1 2018

Fingerprint

Kashin-Beck Disease
Chondrocytes
Glutathione Peroxidase
Methylation
Apoptosis
Phosphatidylinositol 3-Kinases
Selenium
Selenoproteins
Proto-Oncogene Proteins c-fos
Sodium Selenite
Cell Line
Polymerase Chain Reaction
Proteins
Fluorescein-5-isothiocyanate
Annexin A5
Blood Cells
Oxidative Stress

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

Cite this

Han, L. X., Yang, X. L., Sun, W. Y., Li, Z. F., Ren, H., Li, B. R., ... 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

The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis. / Han, Li Xin; Yang, Xiao Li; Sun, Wen Yan; Li, Zhao Fang; Ren, Hao; Li, Bao Rong; Zhang, Rong Qiang; Zhang, Dan Dan; Shi, Zi Yun; Liu, Ji Feng; Cao, Jun Ling; Zhang , Jianjun; Xiong, Yong Min.

In: Bone, Vol. 117, 01.12.2018, p. 15-22.

Research output: Contribution to journalArticle

Han, LX, Yang, XL, Sun, WY, Li, ZF, Ren, H, Li, BR, Zhang, RQ, Zhang, DD, Shi, ZY, Liu, JF, Cao, JL, Zhang , J & Xiong, YM 2018, 'The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis', Bone, vol. 117, pp. 15-22. https://doi.org/10.1016/j.bone.2018.08.017
Han, Li Xin ; Yang, Xiao Li ; Sun, Wen Yan ; Li, Zhao Fang ; Ren, Hao ; Li, Bao Rong ; Zhang, Rong Qiang ; Zhang, Dan Dan ; Shi, Zi Yun ; Liu, Ji Feng ; Cao, Jun Ling ; Zhang , Jianjun ; Xiong, Yong Min. / The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis. In: Bone. 2018 ; Vol. 117. pp. 15-22.
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title = "The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis",
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.",
keywords = "DNA methylation, Glutathione peroxidase 3, Kashin-Beck disease, PI3K/Akt/c-fos signaling pathway, Selenium",
author = "Han, {Li Xin} and Yang, {Xiao Li} and Sun, {Wen Yan} and Li, {Zhao Fang} and Hao Ren and Li, {Bao Rong} and Zhang, {Rong Qiang} and Zhang, {Dan Dan} and Shi, {Zi Yun} and Liu, {Ji Feng} and Cao, {Jun Ling} and Jianjun Zhang  and Xiong, {Yong Min}",
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T1 - The study of GPX3 methylation in patients with Kashin-Beck Disease and its mechanism in chondrocyte apoptosis

AU - Han, Li Xin

AU - Yang, Xiao Li

AU - Sun, Wen Yan

AU - Li, Zhao Fang

AU - Ren, Hao

AU - Li, Bao Rong

AU - Zhang, Rong Qiang

AU - Zhang, Dan Dan

AU - Shi, Zi Yun

AU - Liu, Ji Feng

AU - Cao, Jun Ling

AU - Zhang , Jianjun

AU - Xiong, Yong Min

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - DNA methylation

KW - Glutathione peroxidase 3

KW - Kashin-Beck disease

KW - PI3K/Akt/c-fos signaling pathway

KW - Selenium

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