MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway.

Ji-Jun Zhao,Zhao-Feng Wu,De-Hong Feng,Ling Wang,Li Cheng,Dengshun Miao

doi:10.1371/journal.pone.0159805

Abstract

ObjectiveTo investigate the role of microRNA-145 (miR-145) in steroid-induced necrosis of the femoral head (SINFH) by evaluating its effects on the OPG/RANK/RANKL signaling pathway.MethodsA rat model of SINFH was constructed via injection of the lentiviral vector pLV-shRNA-miR-145. Pathological observation was performed via tartrate-resistant acid phosphatase (TRAP) staining, and serum OPG levels were detected by ELISA. The mRNA expression levels of miR-145, OPG, RANK and RANKL in THP-1 cells were assessed by RT-PCR, and the protein expression levels of OPG, RANK and RANKL were assessed by western blotting.ResultsThe expression of miR-145 in the lentivirus-mediated miR-145 group was significantly up-regulated compared with that in the control and normal groups (both P < 0.01). Serum OPG levels were decreased in SINFH rats compared with control and normal rats. The mRNA and protein expression levels of OPG in THP-1 cells decreased after transfection (all P < 0.05). By contrast, the mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection (all P < 0.05). After transfection of 293T cells with an miR-145 overexpression vector, miR-145 expression in 293T cells increased significantly, while OPG mRNA and protein expression decreased significantly (all P < 0.05).ConclusionMiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.

Highlights

Osteonecrosis (ON) of the femoral head is a potentially debilitating disease that frequently affects young people [1, 2]
Serum OPG levels were decreased in steroid-induced necrosis of the femoral head (SINFH) rats compared with control and normal rats
The mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection

Summary

Introduction

Osteonecrosis (ON) of the femoral head is a potentially debilitating disease that frequently affects young people [1, 2]. Steroid-induced necrosis of the femoral head (SINFH), which is induced by high doses and/or long-term administration of steroid hormones, is one of the most serious complications of steroid administration [6,7,8]. Fatty marrow is a well-established early histological manifestation of SINFH in vivo [6]. It has been reported that SINFH occurs in patients who have received corticosteroid treatment for underlying diseases, such as systemic lupus erythematosus, nephrotic syndrome and renal transplantation [9]. There have been many reports of high early failure rates in patients with steroid-induced ON, suggesting that the prognosis of SINFH is poor even after surgical treatment [9, 10]. An effective biomarker for diagnosing and treating SINFH is urgently needed

Methods

Results

Conclusion