牵张应力介导TGF-β1/Smad7信号通路相关microRNAs调控人牙周膜细胞成骨分化的研究

Studies on the mechanisms of periodontal ligament cells osteogenic differentiation under mechanical stimulation are essential to promote better understanding of the orthodontic periodontal tissue remodeling. We have previously shown that TGF-β1/Smad7 signaling participated into the regulating process of human periodontal ligament cells osteogenic differentiation. However, the molecular mechanisms that regulate TGF-β1/Smad7 signaling by mechanical stretch require further investigation. Recent studies have shown that microRNAs play critical roles in cell differentiation by controlling signaling molecules gene expression of their related signaling pathways during osteogenesis. Therefore, in this project, based on our previous research results,by useing the cell-mechanical stretch culture model combined with microRNA microarray chip, quantitative real time PCR, RNA interference, dual luciferase reporter assay and bioinformatic analysis methods, we will investigate the interaction between TGF-β1/Smad7 signaling molecules and their related microRNAs, and study the effect of microRNAs targeted to regulate the TGF-β1/Smad7 on the osteogenic differentiation process, and explore the molecular mechanisms of TGF-β1/Smad7signaling pathway and related microRNAs in regulating osteogenic differentiation of human periodontal ligament cells stimulated by mechanical stretch.This study will provide novel insights into the molecular mechanism of the orthodontic periodontal tissue remodeling.

研究牵张应力状态下牙周膜细胞成骨分化调控机制对于理解正畸牙周组织的改建具有重要意义。前期研究发现，在机械牵张应力作用下，TGF-β1/Smad7信号通路参与了人牙周膜细胞成骨分化的调节，然而牵张应力对该信号通路调控的机制并不清楚。近年研究认为，microRNAs通过对信号通路及其相关信号分子的调节作用，调控细胞的成骨分化过程。因此，本研究拟在前期研究的基础上，通过建立体外人牙周膜细胞牵张应力培养模型，采用MicroRNAs芯片检测、实时定量RT-PCR，RNA干扰、双荧光素酶报告基因检测及生物信息学方法等技术，研究牵张应力作用下,TGF-β1/Smad7信号通路及其相关microRNAs的相互作用及靶向调节TGF-β1/Smad7的microRNAs对人牙周膜细胞成骨分化的影响，探讨在牵张应力作用下，TGF-β1/Smad7信号通路相关microRNAs调控人牙周膜细胞成骨分化的分子机制。