槲皮素/介孔生物活性玻璃缓释系统介导巨噬细胞miR-21a-5p/PDCD4/NF-κB通路调控牙周炎骨缺损修复的研究

牙周炎骨缺损的修复是治疗重度牙周炎的关键，其难点在于持续有效抑制缺损部位炎症反应，同时促进牙槽骨骨髓间充质干细胞（BMSCs）、牙周膜干细胞（PDLSCs）的成骨分化。课题组前期研究证实槲皮素能够调控BMSCs成骨/成血管分化并抑制炎性因子表达、促进PDLSCs增殖；预实验还发现槲皮素能下调炎性巨噬细胞miR-21a-5p表达并沉默其下游PDCD4基因。可见槲皮素具有抑制炎症反应、调控炎症微环境下BMSCs和PDLSCs生物学效应及巨噬细胞免疫功能；并可能通过介导巨噬细胞miR-21a-5p/PDCD4/NF-κB通路调控牙周炎骨缺损修复，但仍有待证实。本课题旨在开展槲皮素/介孔生物活性玻璃缓释系统的构建，通过槲皮素长效可控释放以实现持续性的抑制炎症反应并促进牙周炎骨缺损修复，同时揭示其相关机制。本课题的实施有望为牙周炎骨缺损修复提供新的策略，具有重要的科学意义和应用价值。

It is the key to repair bone defect for the treatment of severe periodontitis. The difficulty lies in how to continuously and effectively inhibit the inflammatory reaction in the defect site, meanwhile, promote the osteogenic differentiation of alveolar bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament stem cells (PDLSCs). Our recent studies have found that quercetin could regulate the osteogenic/angiogenic differentiation of BMSCs, inhibit the expression of inflammatory cytokines and promote the proliferation of PDLSCs, while preliminary experiments also found that quercetin could downregulate the expression of the miR-21a-5p and silence the downstream PDCD4 gene of inflammatory macrophages. These results suggest that quercetin could inhibit inflammatory reaction, regulate the biological responses of BMSCs and PDLSCs under inflammatory microenvironment, and also possess an immunomodulatory effect on macrophages. And quercetin might achieve periodontitis bone defect repair via regulating the miR-21a-5p/PDCD4/NF-κB pathway of macrophages, which remains to be further confirmed. This research is aim at constructing quercetin/mesoporous bioactive glass sustained-release system, through the long-term controlled release of quercetin to achieve sustained inhibition of inflammatory reaction and promote periodontitis bone defect repair, meanwhile, to reveal its related mechanism. Implementation of this research might provide a new strategy for periodontitis bone defect repair, which has important scientific significance and application value.