牙周缺损是成人牙齿缺失的首要原因，如何有效修复牙周缺损是研究者一直面对的难题。研究表明，细胞膜片在缺损牙周组织的修复中有良好运用前景，其修复过程受到Fas/FasL等多种信号通路调控。Fas/FasL是成骨分化的重要信号通路之一，Fas及FasL表达降低能促进成骨细胞分化。课题组前期研究发现，Let-7a能抑制骨髓间充质干细胞Fas及FasL的表达，且Fas/FasL表达降低，能增强骨髓间充质干细胞自噬水平，促进成骨分化。因此，是否可通过Let-7a抑制Fas/FasL信号通路，促进骨髓间充质干细胞膜片自噬，增强其成骨能力，进而运用于治疗牙周组织缺损？本研究拟上调/抑制骨髓间充质干细胞膜片Let-7a的表达，在动物模型中对比其体内成骨效能及修复牙周缺损的能力，并验证相关分子通路Fas/FasL及骨髓间充质干细胞膜片自噬水平的改变，从而为研究更好的再生修复缺损牙周组织提供新的思路与方法。

Periodontal defect is a major cause for tooth loss for adults, how to repair periodontal defects effectively is the problem which researchers should be faced with. Studies have shown that cell-sheet has a good application prospect in repairing periodontal defects. A variety of molecular signal pathways regulating the repair process, and Fas/FasL signaling pathway is one of the most important signaling pathways in regulation of osteogenic differention, absence of Fas or FasL can stimulate osteoblastic differentiation. Ours research previously showed that Let-7a inhibits both Fas and FasL protein accumulation of bone marrow mesenchymal stem cells, Fas/FasL expression reduced can enhance the bone marrow mesenchymal stem cells autophagy level promoting osteogenesis differentiation. Therefore, in this study we will determine whether Let-7a could promote autophagy of bone marrow mesenchymal stem cell sheet to enhance its osteogenesis ability through inhibiting Fas/FasL signaling pathway and then could be applied in treating periodontal tissue defect? So, we intend to increase or inhibit the expression of Let-7a of bone marrow mesenchymal stem cell sheet to compare the ability of bone formation in vivo, repair the periodontal tissue defects in animal models and to verify the change of Fas/FasL pathway and autophagy. Thus, this could provide new ideas and methods for repairing and regenerating periodontal tissue defect.