LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation

Qingyu Wang,Qiwei Yang,Guizhen Zhang,Zhenwu Du,Haiyue Zhao,Zhaoyan Li,Yang Song,Ming Ren,Ao Wang,Gaoyang Chen

doi:10.1038/s41598-018-27501-2

Abstract

Long noncoding RNAs (lncRNAs) are critical gene expression regulators and are involved in several bone diseases. To explore the potential roles of lncRNAs in osteonecrosis of the femoral head (ONFH), we investigated for the first time the lncRNA expression profile of bone marrow mesenchymal stem cells (BMSCs) from patients with steroid-induced ONFH (SONFH) with microarray and bioinformatics analysis. A total of 1878 lncRNAs and 838 mRNAs were significantly up-regulated while 1842 lncRNAs and 1937 mRNAs were statistically down-regulated in the SONFH group compared with control group. The results validated by qRT-PCR were consistent with the microarray profiling data, especially involved in upregulation and downregulation of critical lncRNAs as well as mRNAs expression related to adipogenic and osteogenic differentiation. Pathway analyses revealed 40 signaling pathways with significant differences, especially the signaling pathways to regulate stem cell pluripotency. The CNC and ceRNA network indicated that lncRNA RP1-193H18.2, MALAT1 and HOTAIR were associated with abnormal osteogenic and adipogenic differentiation of BMSCs in the patients with SONFH. Our results suggest the lncRNA expression profiles were closely associated with the abnormal adipogenic and osteogenic transdifferentiation of BMSCs during the development of SONFH and explore a new insight into the molecular mechanisms of SONFH.

Highlights

Osteonecrosis of the femoral head (ONFH) is a multifactorial and disabling disease that involves multiple genetic and environmental factors[1,2]
ONFH is considered as a stem cell disease, which is associated with imbalance osteogenesis and adipogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs), and the upregulation of adipogenic differentiation may play an essential role on the lipopexia of ONFH15
Osteoblasts and adipocytes are originated from a common progenitor cell of BMSCs

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a multifactorial and disabling disease that involves multiple genetic and environmental factors[1,2]. Excess steroid use has been recognized as one of environmental risk factors and steroid-induced osteonecrosis of the femoral head (SONFH) is considered as a disease of abnormal BMSC transdifferentiation due to the roles of steroid in promotion of adipogenic differentiation and inhibition of osteogenic differentiation of BMSCs7,8. The biological role of lncRNA expression profiles in the abnormal adipogenic and osteogenic transdifferentiation of BMSCs in ONFH has not been reported.

Methods

Results

Conclusion