He Yani, Guan Xiaoyue, Du Yang, Liu Guanzhi, Li Yingxue, Wei Zhichen, Shi Chen, Yang Jianmin, Hou Tiezhou
The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University Xi'an 710004, Shaanxi, P. R. China.
Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University Xi'an 710004, Shaanxi, P. R. China.
Am J Transl Res. 2021 Oct 15;13(10):11126-11143. eCollection 2021.
MicroRNAs (miRNAs) have been demonstrated as crucial transcriptional regulators in proliferation, differentiation, and tumorigenesis. The comprehensive miRNA profiles of osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) under the condition of mechanical stress remains largely unknown. In this study, we aimed to discover the miRNA expression profiles of hDPSCs exposed to mechanical stress under the osteogenic/odontogenic process. We found that mechanical stress (0.09 MPa and 0.18 MPa, respectively, 30 min/day) significantly promoted the proliferation of hDPSCs since the fifth day. The expressions of DSPP, DMP1, and RUNX2 were significantly increased on day 7 in the presence of 0.09 MPa and 0.18 MPa mechanical stress. On day 14, the expression levels of DSPP, DMP1, and RUNX2 were decreased in the presence of mechanical stress. Among 2578 expressed miRNAs, 5 miRNAs were upregulated and 3 miRNAs were downregulated. Six hub target genes were merged in protein-protein interactions (PPI) network analysis, in which existed only one sub-network. Bioinformatics analysis identified an array of affected signaling pathways involved in the development of epithelial and endothelial cells, cell-cell junction assembly, Rap1 signaling pathway, regulation of actin cytoskeleton, and MAPK signaling pathway. Our results revealed the miRNA expression profiles of osteogenic/odontogenic differentiation of hDPSCs under mechanical stress and identified eight miRNAs that were differentially expressed in response to the mechanical stress. Bioinformatics analysis also showed that various signaling pathways were affected by mechanical stress.
微小RNA(miRNA)已被证明是增殖、分化和肿瘤发生过程中的关键转录调节因子。在机械应力条件下,人牙髓干细胞(hDPSC)成骨/成牙本质分化的全面miRNA谱在很大程度上仍不清楚。在本研究中,我们旨在发现成骨/成牙本质过程中受到机械应力的hDPSC的miRNA表达谱。我们发现,自第5天起,机械应力(分别为0.09MPa和0.18MPa,每天30分钟)显著促进了hDPSC的增殖。在存在0.09MPa和0.18MPa机械应力的情况下,第7天DSPP、DMP1和RUNX2的表达显著增加。在第14天,存在机械应力时DSPP、DMP1和RUNX2的表达水平下降。在2578个表达的miRNA中,5个miRNA上调,3个miRNA下调。在蛋白质-蛋白质相互作用(PPI)网络分析中合并了6个枢纽靶基因,其中仅存在一个子网。生物信息学分析确定了一系列受影响的信号通路,这些信号通路参与上皮和内皮细胞发育、细胞-细胞连接组装、Rap1信号通路、肌动蛋白细胞骨架调节和MAPK信号通路。我们的结果揭示了机械应力下hDPSC成骨/成牙本质分化的miRNA表达谱,并鉴定了8个响应机械应力而差异表达的miRNA。生物信息学分析还表明,各种信号通路受到机械应力的影响。