Treg/Th17平衡对2型糖尿病颅颌骨缺损再生与修复的影响及机制研究

项目名称： Treg/Th17平衡对2型糖尿病颅颌骨缺损再生与修复的影响及机制研究

项目编号： No.81500812

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： 唐健霞

作者单位： 中南大学

项目金额： 18万元

中文摘要： 2型糖尿病患者颅颌骨缺损的再生修复是口腔医学的难题，主要原因是其再生障碍的免疫及分子机制不清，是亟待解决的关键科学问题。以往报道Treg/Th17平衡能够调控骨再生，本课题组前期研究发现骨髓干细胞具有调节Treg/Th17的能力，糖尿病小鼠骨髓干细胞免疫调控功能的异常导致机体免疫功能受损。但Treg/Th17功能异常对2型糖尿病颅颌骨再生障碍的影响及机制尚不清楚。本课题拟利用糖尿病小鼠模型在体内外研究Treg/Th17平衡与失衡对骨髓干细胞分化、免疫等功能及对2型糖尿病颅颌骨再生的影响及分子调控机制；探讨糖尿病常规用药-二甲双胍是否可通过上述机制改善骨髓干细胞免疫调节功能，进而促进2型糖尿病颅骨缺损再生。通过本研究将进一步阐明2型糖尿病颅颌骨缺损再生障碍的免疫及分子机制，拓展二甲双胍这类糖尿病常规用药的用途，为促进2型糖尿病患者颅颌骨再生修复的临床治疗提供理论依据及实验数据。

中文关键词： 间充质干细胞；分子机制；免疫机制；骨再生；糖尿病

英文摘要： It is a major challenge for repair of calvarial and jaw defects with type 2 diabetes (T2D) in dental field, because the immune and molecular mechanisms involving in it are still not fully understood, which has become an urgent and critical issue to be resolved. The balance of Treg/Th17 has been reported to regulate bone regeneration, while our previous study has revealed that bone marrow mesenchymal stem cells (BMMSCs) could control the Treg/Th17. We also find that impaired immunomodulatory properties of BMMSCs resulted in disfunction of immune system. However, it is still not clear about the effects and mechanisms of Treg/Th17 dysfunction on repair of calvarial and jaw defects with T2D. Thus, in the present study, we will use T2D mice to study the effects and mechanisms of balance or imbalance between Treg/Th17 on functions of BMMSCs, such as differentiation, immunomodulatory properties, etc, and restoration of calvarial and jaw defects with T2D. Next, we will investigate whether metformin, characterized as one conventional drug to treat diabetes, could improve the immunomodulatory properties of BMMSCs, thus promoting bone regeneration of calvarial and jaw defects with T2D via Treg/Th17. Taken together, our study will discover the immune and molecular mechanisms, involving in impaired bone regeneration of calvarial and jaw defects with T2D, demonstrate new functions and potential applications of metformin, and provide theoretical and experimental evidence for improving restoration of calvarial and jaw defects with T2D in clinic in the future.

英文关键词： mesenchymal stem cells;molecular mechanism;immune mechanism;bone regeneration;diabetes