Abstract

BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is a devastating orthopedic disease, which seriously affects the quality of life of patients. The study aims to investigate the effects of LncRNA NORAD on SONFH.MethodsHuman bone marrow-derived mesenchymal stem cells (hBMSCs) were isolated from the proximal femur of patients during routine orthopedic surgery and then cultured with dexamethasone (Dex) and transfected with NORAD overexpression vector, siRNA-NORAD and miR-26a-5p mimics. The mRNA expression of NORAD, miR-26a-5p, OPG, RANK, and RANKL was detected by RT-qPCR. Cell proliferation and apoptosis was measured by CCK-8 assay and flow cytometry, respectively. The protein expression of RUNX2, OPG, RANK, and RANKL was detected by western blot. The dual-luciferase reporter gene assay was performed to confirm the binding between NORAD and miR-26a-5p.ResultsNORAD expression was downregulated in SONFH tissues, while miR-26a-5p expression was upregulated. Overexpression of NORAD improved DEX-induced inhibition of proliferation and differentiation, and promotion of apoptosis in hBMSCs, while knockdown of NORAD led to the opposite results. Moreover, NORAD improved DEX-induced inhibition of proliferation and differentiation, and promotion of apoptosis by regulation of miR-26a-5p in hBMSCs.ConclusionsNORAD expression was downregulated in SONFH tissues, while miR-26a-5p expression was upregulated. NORAD improved DEX-induced inhibition of proliferation and differentiation, and promotion of apoptosis by regulation of miR-26a-5p in hBMSCs.

Highlights

  • Steroid-induced osteonecrosis of the femoral head (SONFH) is a devastating orthopedic disease, which seriously affects the quality of life of patients

  • LncRNA NORAD expression is downregulated in SONFH tissues and Dex-treated Human bone marrow-derived mesenchymal stem cells (hBMSCs), and treatment of Dex inhibits proliferation and the OPG/RANK/RANKL pathway in hBMSCs We investigated the NORAD expression in bone marrow samples from patients with SONFH and femoral neck fracture by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)

  • We investigated the effects of Dex (0, 10−6, 10−7, and 10−8 M) on NORAD expression, proliferation, and OPG/RANK/RANKL pathway in hBMSCs

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Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (SONFH) is a devastating orthopedic disease, which seriously affects the quality of life of patients. Osteonecrosis of the femoral head (ONFH) is characterized by the collapse of the femoral head due to bone cells and bone marrow to be necrotic [1, 2]. Clinical observation confirmed that most patients who were treated with high-dose GC appeared clinical symptoms of osteonecrosis within 2 years [1]. Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) usually involves young adults and most patients with GIOFH require surgery, which seriously affects the quality of life of patients [5, 6]. The pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) is unclear

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