糖尿病人颅颌面骨缺损是口腔医学亟需解决的难题。阿司匹林乙酰化作用，特别是对组蛋白的乙酰化在代谢性疾病和干细胞分化中至关重要，其详细机制还有待进一步阐明。本项目以模拟糖尿病环境下大鼠骨髓间充质干细胞为研究对象，利用重硫酸盐测序、ChIP、Real time PCR、Western blot、免疫荧光、Micro CT等多种实验方法，从分子、细胞和组织水平多方面探讨。阐明阿司匹林在高糖环境下对骨髓间充质干细胞组蛋白的影响，从细胞增殖、分化、凋亡等方面观察细胞功能，进而模拟体内组织中缺损区域干细胞的功能变化；并针对关键转录因子Runx2启动子区的表观遗传修饰进行研究，以期找到阿司匹林在染色质重组过程中具体的组蛋白作用位点；从短时间组织内干细胞的转归和长期的成骨情况来观察并评价阿司匹林的作用。为阿司匹林这类乙酰化药物在代谢性疾病组织再生领域的研究从表观遗传学的角度提供一定的理论支持。

Because local and metabolic factors block the regeneration of bone tissue, the repair of oral and maxillofacial defects in diabetic patients is a big challenge in stomatology. Acetylation of aspirin, especially on histone, is essential in metabolic diseases and differentiation of stem cells. The specific mechanisms need to be further clarified. Rat BMSCs (bone marrow mesenchymal stem cells) were used in this study, with high glucose cell culture (analog diabetes).The methods of bisulfite sequencing method, ChIP technology, Real time PCR, Western blot, immunofluorescence, Micro CT et al will be used to testify the action mechanism of aspirin in diabetic models. And elucidate the effects of aspirin on histone of BMSCs in high glucose culture. We will verify the function changes of the cells from aspects of cell proliferation, differentiation and apoptosis. Focusing on the key transcription factor Runx2, we are aiming to find out the acting point of aspirin during the process of chromatin remodling in BMSCs. We will elucidate the effects of aspirin on bone critical defect in diabetic animal model both in short and long term experiments. Our research target is to provide epigenetic theory support on aspirin (and other Acetylation medicine) in the tissue regeneration of metabolic diseases.