Integrated miRNA and mRNA expression profiling of tension force-induced bone formation in periodontal ligament cells
Integrated miRNA and mRNA expression profiling of tension force-induced bone formation in periodontal ligament cells
复制标题
牙周膜细胞张力诱导骨形成的 miRNA 和 mRNA 综合表达谱
DOI：
10.1007/s11626-015-9892-0
复制
发表时间：
2015-09-01
影响因子：
2.1
通讯作者：
Han, Guangli
中科院分区：
文献类型：
--
作者：
Chang, Maolin;Lin, Heng;Han, Guangli
张力诱导的骨形成是一个复杂的生物学过程，受到多种因素的影响，例如miRNAs和基因调控网络。然而，我们对这个复杂过程中的关键基因调控因子及其功能后果知之甚少。本研究旨在从系统生物学角度探讨张力诱导牙周膜细胞成骨过程中microRNA和mRNA表达的整合关系。我们通过微阵列鉴定了818个mRNA和32个miRNA在周期性张力刺激的人牙周膜细胞和对照细胞之间的差异表达。通过miRNA/mRNA网络分析、蛋白质-蛋白质相互作用网络分析和hub分析，我们发现miR-195- 5 p、miR-424- 5 p、miR-1297、miR-3607- 5 p、miR-145- 5 p、miR-4328和miR-224- 5 p是张力诱导骨形成的核心microRNA。WDR 33、HSPH 1、ERBB 3、RIF 1、IKBKB、CREB 1、FGF 2和PAG 1被鉴定为PPI网络的枢纽，表明在该过程中具有生物学意义。通过使用定量实时PCR进一步检测人PDLC和动物样品中的miRNA表达。因此，我们提出了张力诱导的骨形成的模型，其通过miRNA和mRNA的整合来共同调节。这项研究说明了系统生物学方法在分析张力诱导的骨形成作为一个复杂的生物学过程中的好处。我们利用公开资料和我们的实验数据进行综合分析，揭示了张力诱导骨形成的miRNAs协同转录调控机制。
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.