GDF11在T2DM拔牙创愈合血管化与骨化过程中的调控作用及机制研究

目前我国2型糖尿病（T2DM）患者人数已超1.04亿，T2DM患者拔牙创愈合不良是导致其种植手术失败风险增高的重要原因。拔牙创愈合包括血管化与骨化两个关键过程。T2DM状态下内皮祖细胞（EPC）成血管与间充质干细胞（MSC）成骨能力降低，进而干扰拔牙创愈合的血管化与骨化过程，但其中的具体机制尚不清楚。近期文献指出TGF-β家族成员GDF11在T2DM骨愈合过程中发挥着重要作用。我们前期研究表明T2DM拔牙创内GDF11表达异常上升；使用GDF11干预能够促进T2DM-EPC血管化，抑制T2DM-MSC成骨分化，提高拔牙创愈合前期血管化程度，抑制后期骨化程度。因此我们推测GDF11是调控T2DM拔牙创愈合血管化与骨化过程的重要开关因子。我们拟利用T2DM家兔拔牙模型探索GDF11调控T2DM状态下拔牙创血管化与骨化过程的作用及机制，为促进T2DM患者拔牙创愈合，降低种植手术失败风险提供依据。

Until 2019, the number of patients with type 2 diabetes mellitus (T2DM) has exceeded 104 million in China. The undesirable tooth extraction socket healing in T2DM patients is one of the important factors responsible for the increased risk of implant failure. Socket healing includes two key processes: the initial vascularization and the following ossification. The vascularization capacity of endothelial progenitor cells (EPC) and osteogenic differentiation capacity of mesenchymal stem cells (MSC) decreased under T2DM condition, thus interfering the vascularization and ossification processes of socket healing. However, the specific mechanism is unclear. Recent studies have indicated that GDF11, one belonging to the TGF-β family, acts as an important role in bone healing under T2DM condition. Our previous study showed that GDF11 expression was abnormally increased in T2DM socket, and inhibition of GDF11 could ameliorate the deficient socket healing. Supplement of GDF11 could promote the vascularization of T2DM-EPC and inhibit the osteogenic differentiation of T2DM-MSC, thus improving the initial vascularization quality and suppressing the ossification quality during socket healing. Therefore, we speculate that GDF11 is an important switch factor for regulating the vascularization and ossification process during T2DM tooth extraction socket healing. With help of the incisor extraction model of T2DM rabbits, we intend to systematically explore and analyze the role and mechanism of GDF11 in the initial vascularization process and the following ossification process during socket healing under T2DM condition, so as to provide research basis for promoting socket healing and reducing the risk of implant failure for T2DM patients.