炎症微环境下miR-511调控TLR4促进人牙周膜干细胞成骨分化的机制研究

Latest study found that PDLSCs can be separated out in inflammation periodontal tissue, owning the potential ability of regenerating cementum and periodontal membrane. Periodontal local inflammatory microenvironment could lead to periodontal tissue regenerated ability destruction through inhibiting the PDLSCs, but the specific mechanism is still not clear. Toll-like receptor can induce the expression of inflammatory cytokines, including some of the immune effector molecules, and TLR4 participate in the inflammatory reaction. However, it needs further study that the role of TLR4 in chronic inflammatory periodontal disease and osteogenic differentiation of PDLSC. More and more study showed that miRNA can regulate the periodontal ligament stem cells and related molecular changes of periodontal membrane properties. We have previously found that miR511 can regulate TLR4 expression through bioinformatics method. This project intends to discuss the role of miR511 regulating TLR4 signal pathway in the osteogenic differentiation of PDLSC, thus to further clarify the molecular mechanisms of TLR4 related functions and improve the level of diagnosis and treatment of the disease.

牙周膜组织中的人牙周膜干细胞（PDLSCs）具有再生牙骨质和牙周膜组织的潜能。牙周局部炎症微环境可以通过抑制PDLSCs的再生能力导致牙周组织的破坏。Toll样受体4（TLR4）可诱导包括炎性细胞因子在内的某些免疫效应分子表达，参与组织细胞凋亡过程及体内缺血再灌注损伤的炎症反应，然而其在牙周炎性微环境中PDLSC成骨分化中的作用及分子机制仍不明确。前期研究结果发现牙周炎组织中miR511可调控TLR4的表达。本研究拟利用牙周炎来源的PDLSCs作为炎症微环境作用下的细胞模型，结合 miR511调控TLR4信号通路在干细胞骨向分化过程中的作用机制，探讨炎症微环境影响干细胞再生能力的分子机制，以期为口腔组织工程学筛选促进牙周炎牙周组织修复的种子细胞和调控因子提供新的理论依据。研究成果将有助于提出合适的模型来使基本的科学信息转化为临床的应用，具有广阔的应用前景。

牙周膜组织中的人牙周膜干细胞（PDLSCs）具有再生牙骨质和牙周膜组织的潜能。牙周局部炎症微环境可以通过抑制PDLSCs的再生能力导致牙周组织的破坏。Toll样受体4（TLR4）可诱导包括炎性细胞因子在内的某些免疫效应分子表达，参与组织细胞凋亡过程及体内缺血再灌注损伤的炎症反应，然而其在牙周炎性微环境中PDLSC成骨分化中的作用及分子机制仍不明确。本研究采用生信预测找到Circ-MAP3K11与miR-511的，存在靶向调控关系。利用牙周炎来源的PDLSCs作为炎症微环境作用下的细胞模型，结合 Circ-MAP3K11-miR511调控TLR4信号通路在干细胞骨向分化过程中的作用机制，抑制miR-511表达会显著增加细胞增殖，降低细胞凋亡，促进成骨分化；抑制Circ-MAP3K11表达会显著降低细胞增殖，促进细胞凋亡，减少成骨分化；故Circ-MAP3K11可以作为牙周炎PDLSCs成骨分化的新的标记物，以期为口腔组织工程学筛选促进牙周炎牙周组织修复的种子细胞和调控因子提供新的理论依据。