牙髓组织受到炎症损伤后，修复性牙本质形成过程常伴有低氧。内质网应激是细胞面对应激的适应性反应，有研究证明低氧时细胞通过内质网应激调控生命活动并参与成骨细胞分化和骨形成。课题组前期发现低氧促进牙髓细胞成牙本质分化，并上调内质网应激水平。牙髓干细胞成牙本质分化与成骨细胞分化相似，因此推测低氧介导内质网应激参与调控牙髓干细胞成牙本质分化，这可能是牙髓干细胞分化的一个新机制。为证实此假设，拟运用RNA干扰/基因过表达关键信号分子下调/上调内质网应激，检测低氧时牙髓干细胞成牙本质分化情况；并利用生物信息技术、染色体免疫共沉淀和荧光素酶报告基因系统等探讨低氧时内质网应激关键信号分子与成牙本质分化标志分子的相互作用，初步阐明其分子机制。同时将基因修饰细胞与生物支架材料复合观察体内牙本质形成能力，进一步明确内质网应激调控牙髓干细胞成牙本质分化，从而丰富牙髓干细胞分化理论，以期为活髓保存治疗提供新策略。

Hypoxia usually occurs in the process of raparative dentinogenesis, when dental pulp suffers from inflammation or injury.Endoplasmic reticulum （ ER ）stress which is an important cell's response to stress, is proved to regulate cell's life activity in hypoxia and osteoblast's differentiation and bone formation. In our previous study, we found that hypoxia promoted the odontogenic differentiation of dental pulp cells. In the meantime, ER stress level of dental pulp cells was increased by hypoxia. It is well known that odontogenic differentiation is similar to osteoblast differentiation. Therefore, we hypothesize that hypoxia mediated ER stress regulates dental pulp stem cell(DPSC)'s odontogenic differentiation. To prove this hypothesis, shRNA and gene overexpression technologies will be used to down or up cells' ER stress levels and DPSC's odontogenic differentiation will be detected in hypoxia condition. Moreover, the interaction between ER stress and odontogenic differentiation markers, which can explore the mechanism preliminarily, will be investigated by some techniques such as biological information technology, chromatin immunoprecipitation and luciferase reporter system. Meanwhile, gene modified cells will be combined with the scaffold biomaterials to detect the cells'odontogensis ability in vivo. Above all, the goal of this study is to confirm that hypoxia mediated ER stress regulates DPSC's odontogenic differentiation, which will enrich the theroies of DPSC's odontogenic differentiation and provide new strategy for therapies of dental pulp conservation .