DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head

Menghu Sun,Yuju Cao,Xiaolong Yang,Feimeng An,Jianzhong Wang,Huiqiang Wu

doi:10.1186/s12891-021-04472-6

Abstract

BackgroundDysregulation 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.MethodsA 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.ResultsIn 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.ConclusionMethylation 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.

Highlights

Dysregulation of the OPG/Receptor activator of nuclear factor-κ B (RANK)/RANKL signalling pathway is a key step in the occurrence of steroidinduced osteonecrosis of the femoral head (ONFH)
The case group was composed of patients who were diagnosed with steroidinduced Osteonecrosis of the femoral head (ONFH) during hospitalization and were classified using the latest Association Research Osteocirculatory System (ARCO) [13]
Through the above comparative analysis, we found that the methylation status of the OPG, RANK, and RANKL genes was different between patients and healthy subjects

Summary

Introduction

Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroidinduced 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. Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is a disease primarily due to the extensive use of hormones. The incidence of steroid-induced ONFH is increasing every year, and it is one of the most common non-traumatic ONFHs, accounting for approximately 24.1% of the total number of patients with ONFH [2]. The early diagnosis of this disease is difficult, and it often progresses to the late stage, requiring hip replacement surgery, which seriously affects the quality of life of patients [3]. The early diagnosis and treatment of the disease is the focus of current research.

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