Expression profile analysis of lncRNA in bone marrow mesenchymal stem cells exosomes of postmenopausal osteoporosis patients through microarray and bioinformatics analyses

Abstract

Background: Postmenopausal osteoporosis (PMOP) is the most common bone metabolic disease affecting women worldwide. In this study, we investigate the role of long non-coding RNA (lncRNA) expression in exosomes obtained from bone marrow mesenchymal stem cells (BMSCs) of patients with PMOP.

Methods: BMSCs from patients diagnosed with PMOP and healthy post-menopausal females as controls were isolated and cultured before exosome extraction. RNA microarray technology was used to identify differentially expressed lncRNAs in exosomes from BMSCs. Bioinformatics technology was utilized to analyze the roles of differentially expressed lncRNAs. Further, RT-qPCR was used to validate differentially expressed lncRNAs in 20 pairs of clinical samples.

Results: A total of 286 differentially expressed lncRNAs were detected in the exosomes from BMSCs unlike in the control group, among which 148 were up-regulated, whereas 138 were down-regulated. RT-qPCR identified five critical lncRNAs, including ENST00000593078, NR_120593, ENST00000422343, MEG3 and NR_029192. This was consistent with the microarray results and with a significant difference (P < 0.01). Based on the differentially expressed lncRNAs, we constructed lncRNA-miRNA-mRNA interaction networks. Functional analysis revealed that differentially expressed lncRNAs in patients with PMOP potentially target Wnt/β-catenin, MAPK, and PI3K-Akt pathways.

Conclusion: In summary, we detected several dysregulated lncRNAs regulating PMOP progression in exosomes extracted from BMSCs of affected patients acting as novel biomarkers. This in turn provides valuable data for targeted treatment of PMOP.

Subjects: Genomics; Molecular biology; Orthopedics; Women's Health.

Keywords: Bone marrow mesenchymal stem cells; Exosome; LncRNA; Microarray; Postmenopausal osteoporosis.