BMAL1调控间充质干细胞在糖尿病性牙周炎骨缺损修复的机制

项目名称： BMAL1调控间充质干细胞在糖尿病性牙周炎骨缺损修复的机制

项目编号： No.81470754

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭斌

作者单位： 中国人民解放军总医院

项目金额： 67万元

中文摘要： 牙周炎和2型糖尿病是发生于老年人中的相互关联、协同破坏的两种慢性高发性疾病，而牙周组织重建是治疗牙周炎、防止感染对糖尿病患者造成危害的关键。近年来发现，近日钟基因BMAL1与衰老、糖尿病治疗的时间生物学存在联系。课题组前期研究表明，糖尿病大鼠牙龈组织中BMAL1的表达降低。高糖下，糖尿病大鼠和健康大鼠骨髓间充质干细胞（BMSCs）增殖和成骨分化标志物表达受抑制，但BMAL1对糖尿病状态下BMSCs成骨能力影响的作用机制有待进一步研究。本研究拟通过体外及体内实验探讨钟基因BMAL1表达与糖尿病性牙周炎状态下BMSCs增殖及骨向分化能力的机制。通过分离培养糖尿病性牙周炎GK大鼠BMSCs，采用慢病毒转染增强BMAL1的表达，检测相关通路关键调节因子的变化，接种于壳聚糖/β-甘油磷酸钠植入牙周骨缺损区，观察比较各组牙周缺损修复效果，为防治糖尿病性牙周炎骨缺损寻找新的靶点提供医学理论依据。

中文关键词： 糖尿病性牙周炎；近日钟基因；间充质干细胞；成骨分化

英文摘要： Diabetic periodontal disease, high prevalent in aged people, is characterized by severe destruction of periodontal tissues. The key to treating diabetic periodontitis is to regenerate periodontal tissue in an effective and permanent way. Rencently, it is indicated that there is strong connection between circadian clock gene BMAL1 and caducity. According to our previous studies,the expression of BMAL1 in the gingiva in rats with diabetic periodontitis is weakened. The expression of biomarkers of proliferation and osteogenic differentiation of BMSCs in both diabetic and normal rats is down-regulated in high-glucose cultures. But the mechanism and the relationship BMAL1 regulating the osteogenic alteration of MSCs in diabetic periodontitis remain unclear. This study is to investigate the effects on the proliferation and differentiation capacity of BMSCs from type 2 diabetic periodontitis by enhancing expression of clock genes BMAL1 in vitro and in vivo, and to clarify the possible mechanism involved in the impaired osteogenic ability and periodontal deterioration. Normal BMSCs are transfected by lentiviral vectors enhancing the expression of BMAL1 and lentiviral vectors without the target gene BMAL1, seeded in chitosan / β-glycerophosphate or not. Then the compound is implanted in daibetic periodontal bone defects, while the control group without any treatment. Periodontal repair, osteogenic markers, bone matrixes calcification, adverse diabetic and periodontal markers are observed and analyzed. Based on these, we propose this study to investigate the relationship among the expression of the circadian clock gene BMAL1, the proliferation of BMSCs and the osteogenic differentiation of MSCs in diabetic periodontitis. Moreover, we hope to find novel targets for diabetic periodontitis skeleton defect prevention and therapy.

英文关键词： diabetic periodontitis;circadian clock gene;mesenchymal stem cells;osteogenic differentiation