Systematic Analysis of Plasma Exosome MiRNA in Patients with Postmenopausal Osteoporosis

Abstract Background: More and more studies have shown that exosomes are involved in many aspects of bone metabolism. As the content of exosomes, miRNA plays an important role in the early diagnosis, treatment and prognosis evaluation of osteoporosis.Objective: To determine the potential molecular markers of osteoporosis by analyzing the differences of plasma exosome miRNA expression between postmenopausal women with osteoporosis and healthy controls.Methods: Serum samples of postmenopausal osteoporosis (PMOP) patients over 65 years old (n = 12) and healthy controls (n = 12) were collected. The exosomes were separated by molecular size exclusion chromatography(SEC).The differentially expressed miRNAs were analyzed by cluster analysis. The target genes of miRNAs were predicted and annotated by relevant software.The target genes were classified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The appropriate biomarkers were screened out.Results: The miRNA spectrum of the patients was significantly different from that of the control group. Validation studies showed that 14 up-regulated miRNAs had a high probability of prediction, which could distinguish osteoporosis patients from healthy controls. Thirty-one genes were predicted to be targets for these miRNAs. GO enrichment analysis showed that miRNAs were mainly concentrated in protein binding, carbohydrate-binding, chromatin binding and protein kinase binding. KEGG enrichment analysis showed that miRNAs were mainly concentrated in the p53 signalling pathway, mineral absorption, glycerin metabolism, insulin secretion, glycosaminoglycan biosynthesis heparin sulfate /heparin pathway. This study identified a large number of differentially expressed miRNAs in plasma samples from postmenopausal women with osteoporosis. It may help to obtain new diagnosis and treatment strategies for PMOP.Conclusion: Our study identified the characteristics of plasma miRNAs in patients with osteoporosis and identified 14 candidate miRNAs, which may be useful biomarkers of osteoporosis. We speculate that these differentially expressed miRNAs may play a key role in the process of bone marrow mesenchymal stem cells osteogenic metabolism and transformation.