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

Abstract

Background: The dysregulation of OPG/RANK/RANKL signaling 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 OPG, RANK and RANKL genes in steroid-related ONFH.Methods: A case-control study was designed, including 50 patients and 50 controls. The Agena MassARRAY platform is used to detect the methylation status of OPG, RANK and RANKL genes in the blood of subjects. The relationship between the methylation level of the CpG site of each gene and the steroid-related ONFH was analyzed.Results: In the CpG islands of the OPG, RANK and RANKL genes of steroid-related ONFH patients, a number of CpG sites with high methylation rate and high methylation level were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, by constructing the receiver operating characteristic (ROC) curve, we also discovered a few hypermethylated CpG sites, which have predictive diagnostic value for steroid-related ONFH.Conclusion: Methylation in the OPG / RANK / RANKL signaling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites can be used as early prediction and diagnostic targets for steroid-related ONFH.

lncRNA FGD5-AS1 Regulates Bone Marrow Stem Cell Proliferation and Apoptosis by Affecting miR-296-5p/STAT3 Axis in Steroid-Induced Osteonecrosis of the Femoral Head

“…It has been reported that the dysregulation of the OPG/ RANK/RANKL signaling pathway is a key step in the occurrence of steroid-induced ONFH [28]. miR-34a has been found to alleviate steroid-induced ONFH through regulating the OPG/RANK/RANKL signaling pathway [29].…”