组蛋白去乙酰化酶调控TLR4信号诱导牙髓干细胞定向分化的分子机制研究

牙髓干细胞(DPSC)分化为成牙本质细胞样细胞（OBLC）是牙髓损伤修复的关键环节。文献报道Toll样受体（TLR）和组蛋白去乙酰化酶（HDAC）在干细胞分化中发挥重要作用。我们发现HDAC1抑制TLR4信号在DPSC分化中的作用，提示HDAC1参与TLR4信号调控DPSC分化。本项目拟在前期研究基础上，构建TLR4或HDAC1基因沉默和过表达的DPSC细胞系，体内外实验研究TLR4和HDAC1在DPSC定向分化中的作用，观察HDAC1对TLR4信号调控DPSC定向分化的影响，明确TLR4信号通路转录因子之间以及转录因子与HDAC1之间相互作用，确定转录因子在靶基因上结合位点。旨在阐明TLR4调控DPSC定向分化为OBLC的分子机制，探讨HDAC1在DPSC定向分化中的作用，对阐明牙髓损伤修复时牙髓干细胞定向分化的分子机制有重要意义，为将来临床活髓保存治疗和DPSC组织工程应用提供新思路。

Dental pulp stem cells(DPSCs) differentiation into odontoblast-like cell (OBLCs) is a key step in the recovery of the injured pulp. Toll-like receptors(TLRs) and histone deacetylases(HDACs) have been reported to be involved in regulation the differentiation of the stem cells. Our results showed that HDAC1 inhibition of the role of TLR4 signaling in differentiation of DPSC, which indicated that HDAC1 was maybe involved in the differentiation of DPSCs regulated by TLR4 signaling. The present project will try to establish two DPSCs cell lines of gene overexpression or the gene silencing of TLR4 or HDAC1, to investigate the role of TLR4 signaling and HDAC1 in directional differentiation of DPSC, to ascertain the effect of HDAC1 on directional differentiation of DPSC induced by TLR4 signaling, to deterime the interaction between transcriptional factors and interaction between transcrition factors and HDAC1, to detect the binding site of transcription factors in downstream target genes promoter. The aim of this project is to elucidate the molecular mechanism of directional differentiation of DPSC into OBLC regulated by TLR4 signaling, to explore the role of HDAC1 in directional differentiation of DPSC. The study would be significant for elucidation the molecular mechanism of the DPSCs directional differentiation into OBLC during the repair of the injured pulp. It also provides a new idea for the clinical conservative treatment of vital pulp and use of DPSC in tissue engineering in future.