Abstract

Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength, and microstructure. Long non-coding RNAs (lncRNAs) are longer than 200 nt, and their functions in osteoporosis is yet not completely understood. We first harvested the bone marrow mesenchymal stem cells (BMSCs) from ovariectomy (OVX) and sham mice. Then, we systematically analyzed the differential expressions of lncRNAs and messenger RNAs (mRNAs) and constructed lncRNA–mRNA coexpression network in order to identify the function of lncRNA in osteoporosis. Totally, we screened 743 lncRNAs (461 upregulated lncRNAs and 282 downregulated lncRNAs) and 240 mRNAs (128 upregulated and 112 downregulated) with significantly differential expressions in OP compared to normal. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses to investigate the functions and pathways of the differential expression of messenger RNAs (mRNAs), a coexpressed network of lncRNA/mRNA. Quantitative PCR (qPCR) validated that the expressions of NONMMUT096150.1, NONMMUT083450.1, and NONMMUT029743.2 were all downregulated, whereas NONMMUT026970.2, NONMMUT051734.2, NONMMUT003617.2, and NONMMUT034049.2 were all upregulated in the OVX group. NONMMUT096150.1, as a key lncRNA in OP, was identified to modulate the adipogenesis of BMSCs. Further analysis suggested that NONMMUT096150.1 might modulate the adipogenesis of BMSCs via the peroxisome proliferator-activated receptor (PPAR) signaling pathway, AMPK signaling pathway, and the lipolysis regulation in adipocyte and adipocytokine signaling pathway. Our study expands the understanding of lncRNA in the pathogenesis of OP.

Highlights

  • Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength and microstructure, which generates fracture risk and exhibits an association with substantial pain, disability, and even death (Kanis et al, 2019)

  • The bone mineral density (BMD) and bone volume (BV)/total volume (TV) of OVX mice were shown to reduce in comparison with the sham group (Figures 1B,C)

  • 743 DElncRNAs were identified in OVX mice, including 461 upregulated Long non-coding RNAs (lncRNAs), and 282 downregulated lncRNAs; the top 10 DElncRNAs were NONMMUT026970.2, NONMMUT010789.2, NONMMUT016319.2, NONMMUT0

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Summary

Introduction

Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength and microstructure, which generates fracture risk and exhibits an association with substantial pain, disability, and even death (Kanis et al, 2019). Several studies indicate that the imbalance differentiation of BMSCs plays a basic role in PMOP. LncRNA itself does not encode protein and regulates gene expression at epigenetic, transcription, and posttranscriptional levels (Dykes and Emanueli, 2017; Wang et al, 2019). Yin et al (2021) reported that lncRNAs (AK039312 and AK079370) exerted an inhibition effect on the differentiation of osteoblast and the formation of bone by suppressing osteogenic transcription factors via targeting miR-199b-5p, activating GSK-3β and in-depth inhibiting the Wnt/β-catenin pathway. Increasing study indicates that lncRNAs exhibit importantly in BMSCs differentiation and osteoporosis. It is not clear on the roles of most lncRNAs in osteoporosis

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