A Comprehensive Analysis of MicroRNAs in Human Osteoporosis

Abstract

MicroRNAs (miRNAs) are single-stranded RNA molecules that control gene expression in various processes, such as cancers, Alzheimer's disease, and bone metabolic diseases. However, the regulatory roles of miRNAs in osteoporosis have not been systematically analyzed. Here, we performed a comprehensive analysis to identify the differentially expressed miRNAs involved in osteoporosis. MiRNAs associated with osteoporosis were collected through literature retrieval and further screened based on specific inclusion and exclusion criteria. The osteoporosis therapeutic targets of miRNAs were obtained by the integration of miRWalk 3.0 database and five human disease therapeutic target databases. Then, the network analysis and functional enrichment analysis of miRNAs and their targets were performed. As a result, 11 eligible miRNAs were identified highly associated with osteoporosis. MiRNA-mRNA network demonstrated there were the complex mutual interactions between miRNAs and their targets. Besides, ADRB2, AR, ESR1, FGFR1, TRAF6, etc., were identified as the top hub genes in protein-protein interaction (PPI) network. Functional enrichment analysis revealed that miRNAs and their targets were mainly mapped on processes associated with bone and immune system, such as bone remolding, bone mineralization, PI3K/AKt, TNF signaling pathways and Th17 cell differentiation. RT-PCR results showed that the expression of miR-335-3p was significantly down-regulated in hind limb unloading (HLU) mice tibia samples compared with controls, the remaining 10 miRNAs were significantly up-regulated after HLU (P < 0.01). In summary, we identified 11 differentially expressed miRNAs and their hub target genes in osteoporosis, which may be novel diagnostic biomarkers for osteoporosis.

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss

“…Here, we further confirmed that miR-138-5p was elevated with age and negatively correlated with osteoblast differentiation and osteogenesis in human tissues, mice and cultured cells (Figure 1 ). In our previous study, we screened and identified several miRNAs, including miR-138-5p, as potential biomarkers or therapeutic targets in human osteoporosis 14 , 34 , 35 . These data suggested that miR-138-5p might play an important role in senile osteoporosis.…”

Role of microRNA Shuttled in Small Extracellular Vesicles Derived From Mesenchymal Stem/Stromal Cells for Osteoarticular Disease Treatment

“…In contrast, another study reported that miR-155 levels are significantly upregulated in human OA cartilage biopsies and primary chondrocytes stimulated by IL-1ß. Moreover, miR-155 overexpression promotes IL-1ß-induced apoptosis and catabolic activity in chondrocytes in vitro (159). Chen et al reported that MSC-sEV-shuttled miR-136-5p promotes chondrocyte migration in vitro and inhibits cartilage degeneration in vivo (Figure 1) both in human chondrocytes in vitro and in mice in vivo (160).…”

“…In contrast, another study reported that miR-155 levels are significantly upregulated in human OA cartilage biopsies and primary chondrocytes stimulated by IL-1ß. Moreover, miR-155 overexpression promotes IL-1ß-induced apoptosis and catabolic activity in chondrocytes in vitro ( 159 ). Chen et al.…”

Menopausal Transition: Prospective Study of Estrogen Status, Circulating MicroRNAs, and Biomarkers of Bone Metabolism

“…The consequences of osteoporosis substantially increase the consumption of medical and economic resources worldwide (3). Until now, many expression profiling studies have revealed that bone remodeling processes are well-tuned at the transcriptional level and controlled by noncoding RNAs, especially long non-coding RNAs and microRNAs (miRNAs) (4)(5)(6).…”