sema3A修饰的ASCs促进2型糖尿病种植体骨结合作用及机制的研究

At present, dental implantation has become an ideal way to restore the missing teeth. However, studies have shown that patients with type 2 diabetes mellitus (T2DM) have significantly higher failure rate of implantation than healthy patients with missing teeth. That osteoblasts and stem cells around plants in T2DM patients cannot induce osteogenesis very well is the key factors of high failure rate of dental implantation. Adipose-derived stem cells ( ASCs ) have attracted people's attention because of its wide origin, convenience, less damage and strong ability of differentiation to osteoblasts. The recent research results in our group have confirmed that ASCs can promote bone healing in the implant area of ADSCs rats. However, mineralization and calcium deposition of ASCs cannot fully meet the implantation needs of patients with T2DM.A latest research has shown that semaphorin 3A (sema3A) can stimulate the differentiation of osteoblasts and accelerate bone regeneration. Therefore, our group propose to wrap ADSCs cells sheet modified by Sema3A around implants, in order to promote the osseointegration of implants in T2DM rats. Through the tissue morphology, cytology and molecular biology to explore sema3A modified ASCs for type 2 diabetes mellitus rats bone combined with promoting effect, and analyzes the promoting implant bone combined with the molecular mechanism of T2DM rats. The aim of the study was to evaluate whether ASCs modified by Sema3A have positive effect on the osseointegration of implants in the T2DM rats and its molecular mechanism through histomorphology, cytology and molecular biology.

种植义齿是最理想的口腔缺牙修复方式，但对于2型糖尿病（T2DM）患者，其种植失败率显著高于健康缺牙患者。T2DM种植体周围成骨细胞成骨能力及干细胞成骨分化能力的减弱是其种植修复失败率增高的关键因素。脂肪来源的干细胞（ASCs）来源广，取材方便，伤害性小，对于成骨细胞有强大的诱导分化能力，本课题组已证实ASCs能促进T2DM大鼠种植骨缺损区的骨愈合。然而ASCs 的骨基质矿化作用和钙沉积尚不能满足T2DM患者种植修复的临床需求，研究表明脑信号蛋白3A （sema3A）能够刺激成骨细胞分化并加快骨组织再生。因此本课题拟明确sema3A修饰的ASCs膜片包裹到种植体周围能否促进T2DM大鼠种植体周围骨结合。并通过组织形态学、细胞学及分子生物学等方面探索sema3A修饰的ASCs对于T2DM大鼠骨结合的促进作用，分析其促进T2DM大鼠种植体骨结合的分子机制，进一步提高T2DM患者种植体周围骨结合。

目前，种植义齿是最理想的牙齿缺失修复方式，但对于2型糖尿病（T2DM）患者，其种植失败率显著高于健康缺牙患者。T2DM种植体周围成骨细胞成骨能力及干细胞成骨分化能力的减弱是其种植修复失败率增高的关键因素。脂肪来源的干细胞（ASCs）来源广，取材方便，伤害性小，对于成骨细胞有强大的诱导分化能力，本课题组已证实ASCs能促进T2DM大鼠种植骨缺损区的骨愈合。然而ASCs的骨基质矿化作用和钙沉积尚不能满足T2DM患者种植修复的临床需求，研究表明脑信号蛋白3A （sema3A）能够刺激成骨细胞分化并加快骨组织再生。我们以不同浓度的sema3A直接处理大鼠ASCs，并使用sema3A基因修饰ASCs，将sema3A修饰后的ASCs膜片包裹到种植体上，观察能否更好的促进T2DM大鼠种植体的骨结合。从细胞学、组织形态学、以及分子生物学层面来探索sema3A基因修饰对ASCs的诱导分化作用，并分析sema3A修饰的ASCs促进T2DM大鼠种植体骨结合的分子机制。研究结果显示ASCs与BMSCs的成骨能力存在差异，一定范围内不同浓度的sema3A对ASCs的增殖都没有明显影响，都能够促进ASCs成骨，且显示出一定的剂量正相关性。我们培养出了ASCs膜片并成功与种植体复合培养，sema3A修饰的ASCs膜片种植体复合物很好地促进了T2DM大鼠种植体骨结合，并初步探索出sema3A提高T2DM种植体结合可能是通过激活了ASCs内的Wnt/β-catenin通路。研究首次将ASCs膜片与sema3A联合应用于促进T2DM患者的种植体骨结合，并初步探究了sema3A促进ASCs成骨分化的分子机制，为提高T2DM缺牙患者种植体骨结合奠定了一定的研究基础。