» Articles » PMID: 34187427

DNA Methylation in the OPG/RANK/RANKL Pathway is Associated with Steroid-induced Osteonecrosis of the Femoral Head

Overview
Publisher Biomed Central
Specialties Orthopedics
Physiology
Date 2021 Jun 30
PMID 34187427
Citations 6
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH.

Methods: A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods.

Results: In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH.

Conclusion: Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.

Citing Articles

Potential efficacy and mechanisms of icariin for the animal model of osteonecrosis of the femoral head.

Xu J, Deng W, Zhu X, Han D, Zheng Y, Zheng Q Front Pharmacol. 2025; 16:1508971.

PMID: 40046737 PMC: 11880249. DOI: 10.3389/fphar.2025.1508971.


Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head.

Li L, Zhao S, Leng Z, Chen S, Shi Y, Shi L Ann Med. 2024; 56(1):2416070.

PMID: 39529511 PMC: 11559024. DOI: 10.1080/07853890.2024.2416070.


Identification of candidate genes and chemicals associated with osteonecrosis of femoral head by multiomics studies and chemical-gene interaction analysis.

Lu X, Wang X, Wang P, Zhu Y, Liu J, Liu G Front Endocrinol (Lausanne). 2024; 15:1419742.

PMID: 39253583 PMC: 11382631. DOI: 10.3389/fendo.2024.1419742.


Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.

Zhang J, Cao J, Liu Y, Zhao H Biomolecules. 2024; 14(6).

PMID: 38927070 PMC: 11202272. DOI: 10.3390/biom14060667.


Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.

Ma Z, Sun J, Jiang Q, Zhao Y, Jiang H, Sun P Front Endocrinol (Lausanne). 2024; 15:1341366.

PMID: 38384969 PMC: 10879930. DOI: 10.3389/fendo.2024.1341366.


References
1.
Walton E, Hass J, Liu J, Roffman J, Bernardoni F, Roessner V . Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research. Schizophr Bull. 2015; 42(2):406-14. PMC: 4753587. DOI: 10.1093/schbul/sbv074. View

2.
Frohlich A, Sirokay J, Fietz S, Vogt T, Dietrich J, Zarbl R . Molecular, clinicopathological, and immune correlates of LAG3 promoter DNA methylation in melanoma. EBioMedicine. 2020; 59:102962. PMC: 7475111. DOI: 10.1016/j.ebiom.2020.102962. View

3.
Fontecha-Barriuso M, Martin-Sanchez D, Ruiz-Andres O, Poveda J, Sanchez-Nino M, Valino-Rivas L . Targeting epigenetic DNA and histone modifications to treat kidney disease. Nephrol Dial Transplant. 2018; 33(11):1875-1886. DOI: 10.1093/ndt/gfy009. View

4.
Kalkan R, Becer E . RANK/RANKL/OPG pathway is an important for the epigenetic regulation of obesity. Mol Biol Rep. 2019; 46(5):5425-5432. DOI: 10.1007/s11033-019-04997-z. View

5.
Ma W, Xin K, Chen K, Tang H, Chen H, Zhi L . Relationship of common variants in VEGFA gene with osteonecrosis of the femoral head: A Han Chinese population based association study. Sci Rep. 2018; 8(1):16221. PMC: 6212426. DOI: 10.1038/s41598-018-34352-4. View