SIRT1对氧化还原状态调控在BMSCs参与种植体骨整合中的作用机制研究

项目名称： SIRT1对氧化还原状态调控在BMSCs参与种植体骨整合中的作用机制研究

项目编号： No.81500890

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张静莹

作者单位： 大连大学

项目金额： 18万元

中文摘要： 骨髓间充质干细胞(BMSCs)骨向分化受抑与种植牙骨整合失败密切相关。干细胞和终末细胞具有不同的胞内氧化还原状态。我们发现SIRT1在BMSCs骨向分化后表达程度降低，但是氧化还原状态与SIRT1相互关系在BMSCs骨向分化和骨整合中的作用机制尚不清楚。本项目将阐明BMSCs骨向分化过程中，细胞内氧化还原状态和SIRT1表达的动态变化规律；揭示胞内、外氧化还原状态改变对BMSCs骨向分化影响及胞内SIRT1的调控作用；利用糖尿病和牙周炎动物模型模拟高氧化应激种植环境，以不同方式干预种植微环境的氧化还原状态，评价BMSCs参与的骨整合效果及SIRT1的作用，建立通过适时、适当干预种植体局部微环境氧化还原状态的方法，提高牙种植体骨整合效率的方法，以期为提高诸如糖尿病等高氧化应激状态患者种植体骨整合效果提供证据支持。

中文关键词： SIRT1；氧化还原；间充质干细胞；牙种植体；骨整合

英文摘要： Impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is related to incomplete osseointegration of dental implants. Stem cells are of different intracellular redox state compared to end-stage cells. We found decreased SIRT1 expression in osteoblasts differentiated from BMSCs, but the interaction between SIRT1 and intracellular redox states and the effects from which on osteogenic differentiation of BMSCs is still illusive. In this proposed schedule, dynamic oscillation of intracellular redox states and corresponding SIRT1 expression in the progress of osteogenic differentiation of BMSCs will be studied. Osteogenic differentiation efficiencies of BMSCs challenged by various intra- and extra-cellular redox states and the related regulation mechanisms of SIRT1 will be explored. Using diabetes and periodontitis animal models to mimic the implanting environment of oxidation stress, we will also carry out the dental implanting experiment under different perturbations through various modes, which can affect the redox states of the microevironment around the implants. Osseointegration efficiencies will be evaluated from different aspects to ascertain functional activities of BMSCs and SIRT1 regulation or response. The results will help us to formulate a recipe to improve osseointegration efficiency in oxidation stress environment by redox state intervention through proper manners at proper time points. The final aim of the plan is to providing an applicable solution to promote osseointegration efficiency for individuals with oxidation stress implanting microenvironment, such as those of diabetes.

英文关键词： SIRT1;Redox;Mesenchymal stem cell;Dental implant;Osteogenesis