Noncoding RNAs in Steroid-Induced Osteonecrosis of the Femoral Head.

Xinjie Wu,Wei Sun,Mingsheng Tan

doi:10.1155/2019/8140595

Abstract

Steroid-induced osteonecrosis of the femoral head (ONFH) is a severe orthopedic disease caused by the long-term administration of glucocorticoids. The main pathological feature of ONFH is the gradually progressive necrosis of bone cells and the bone marrow, ultimately resulting in structural changes or even complete collapse of the femoral head. However, the exact pathogenic mechanism of ONFH remains unknown. Noncoding RNAs (ncRNAs) have emerged as very powerful regulators of gene expression, functioning at both transcriptional and posttranscriptional levels in the pathogenesis of ONFH. Here, we review the current knowledge of the role of ncRNAs, including microRNAs, long noncoding RNAs, and circular RNAs, in the pathogenesis of steroid-induced ONFH. Further focus and validation of these associations can provide new insight into the pathogenic mechanisms at the molecular level to suggest targets for treatment and prevention.

Highlights

Osteonecrosis of the femoral head (ONFH) is characterized by the progressive necrosis of bone cells and the bone marrow, with an estimated incidence of 300,000–600,000 cases in the general population of the United States in the early 2000s [1]. e incidence of newly diagnosed cases of ONFH has remained stable at approximately 20,000 to 30,000 per year [2]
Hao et al [20] found that miR-708 expression is inversely correlated with osteonecrosis and that targeting miR-708 could promote osteogenic differentiation in vitro and effectively antagonized the suppression effect of steroids on osteoblast and adipocyte differentiation through increasing SMAD3 expression, which may result in an interaction between SMAD3 and RUNX2, and consequent activation of the transforming growth factor-beta (TGF-β) signaling pathway
Dai et al [27] found that miR-217 is notably downregulated in the Bone Marrow Mesenchymal Stem Cells (BMSCs) of steroid-induced ONFH patients and that overexpression of miR-217 could significantly promote osteogenic differentiation and proliferation via repressing dickkopf-related protein 1 (DKK1) to promote the nuclear translocation of β-catenin. ese findings indicate a pivotal role of the miR-217/DKK1/ β-catenin pathway in the pathological process of steroidinduced ONFH (Figure 1)

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is characterized by the progressive necrosis of bone cells and the bone marrow, with an estimated incidence of 300,000–600,000 cases in the general population of the United States in the early 2000s [1]. e incidence of newly diagnosed cases of ONFH has remained stable at approximately 20,000 to 30,000 per year [2]. Functions of miRNAs in BMSCs. Gu et al [21] identified 37 differentially expressed miRNAs in the femoral heads of a steroid-induced ONFH rat model.

Results

Conclusion