Integrated miRNA and mRNA expression profiling of tension force-induced bone formation in periodontal ligament cells.

Tension force-induced bone formation is a complex biological process altered by various factors, for example miRNAs and gene regulatory network. However, we know little about critical gene regulators and their functional consequences on this complex process. The aim of this study was to determine the integrated relation between microRNA and mRNA expression in tension force-induced bone formation in periodontal ligament cells by a system biological approach. We identified 818 mRNAs and 32 miRNAs differentially expressed between cyclic tension force-stimulated human periodontal ligament cells and control cells by microarrays. By using miRNA/mRNA network analysis, protein-protein interactions network analysis, and hub analysis, we found that miR-195-5p, miR-424-5p, miR-1297, miR-3607-5p, miR-145-5p, miR-4328, and miR-224-5p were core microRNAs of tension force-induced bone formation. WDR33, HSPH1, ERBB3, RIF1, IKBKB, CREB1, FGF2, and PAG1 were identified as hubs of the PPI network, suggesting the biological significance in this process. The miRNA expression was further examined in human PDLC and animal samples by using quantitative real-time PCR. Thus, we proposed a model of tension force-induced bone formation which is co-regulated through integration of the miRNA and mRNA. This study illustrated the benefits of system biological approaches in the analysis of tension force-induced bone formation as a complex biological process. We used public information and our experimental data to do comprehensive analysis and revealed the coordination transcriptional control of miRNAs of tension force-induced bone formation.