Back to Search
Start Over
CpG methylation of the GPX3 promoter in patients with Kashin-Beck Disease potentially promotes chondrocyte apoptosis.
- Source :
- Journal of Trace Elements in Medicine & Biology; May2022, Vol. 71, pN.PAG-N.PAG, 1p
- Publication Year :
- 2022
-
Abstract
- To determine the methylation levels of CpGs in the GPX3 promoter region and explore their potential effects on the apoptosis of chondrocytes. Blood specimens were collected from 32 participants; 16 KBD patients and 16 healthy subjects. Twenty-five CpGs in the promoter region of GPX3 were identified and detected by MALDI-TOF-MS. Methylation levels of CpGs were compared between KBD patients and healthy subjects as well as among the KBD patients with different degrees. C28/I2 human chondrocytes were treated with tBHP and Na 2 SeO 3. Apoptosis in chondrocytes was examined under a fluorescence microscope. The methylation levels of GPX3 -1_CpG_11 and GPX3 -1_CpG_16 in KBD patients were significantly higher than those of healthy subjects (P < 0.05). The methylation levels of the other CpGs were not significantly different between the two groups (P > 0.05). The methylation level of GPX3 -1_CpG_24 in KBD patients was significantly higher than those of healthy subjects (P < 0.05). MSP-PCR analysis indicated that the methylation rate of KBD group (9.41%) was significantly higher than that of healthy subjects (1.18%), and that GPX3 DNA methylation increased the risk of acquiring KBD 8 fold (OR = 8.000, 95% CI: 1.023–62.580); The mRNA expression of GPX3 in whole blood of KBD patients was lower than that of healthy subjects (P <0.05); Compared with the control group, GPX3, GPX1 and GPX4 mRNA level of the tertbutyl hydroperoxide injury group decreased significantly (P < 0.05), after supplementation with Na 2 SeO 3. The rate of chondrocytes apoptosis was decreased with the increasing of GPX3 and GPX4 mRNA levels (P <0.05) and GPX3 mRNA showed a similar trend without statistically significant (P >0.05). The methylation patterns of CpGs in GPX3 varied in KBD patients. The experiments indicated that the increased methylation of CpGs within the GPX3 promoter may down-regulate the expression of GPX3, thereby reducing the antioxidant function of GPX3 and promoting chondrocyte apoptosis, both of which accelerates the occurrence of KBD. We therefore propose a new understanding of GPX3 's potential epigenetic and genetic mechanisms that contribute to KBD. [ABSTRACT FROM AUTHOR]
- Subjects :
- METHYLATION
HYDROGEN peroxide
DNA methylation
PROMOTERS (Genetics)
APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 0946672X
- Volume :
- 71
- Database :
- Supplemental Index
- Journal :
- Journal of Trace Elements in Medicine & Biology
- Publication Type :
- Academic Journal
- Accession number :
- 155845192
- Full Text :
- https://doi.org/10.1016/j.jtemb.2022.126943