miR-27对上颌窦黏膜骨原细胞成骨分化调控机制的研究

Maxillary sinus floor elevation is effective in solving insufficient alveolar bone in posterior maxilla before dental implant placement. Nevertheless, the slow rate and limited volume of new bone formation under the Schneiderian membrane could influence implant success rate. It's known that osteoprogenitor cells in Schneiderian membrane (OCSM) have the potential of osteogenic activity. However, the specific cellular and molecular mechanisms are still not clear. We've already demonstrated canine OCSM could differentiate into osteoblasts in osteogenic induction medium, and canine sinus mucosa could generate bone tissue in maxillary sinus floor elevation. In addition, we have found miR-27 involved in osteogenic differentiation process of OCSM. All the findings suggested miR-27 might play an important role in maxillary sinus floor augmentation. On the basis of the aforementioned research work, we intend to figure out: ①The target genes and target sites of miR-27 in osteogenic differentiation process of OCSM; ②The osteogenic signaling pathways which miR-27 participate in osteogenic differentiation process of OCSM. Through this project is expect to reveal the mechanisms of miR-27 in maxillary sinus bone formation. Importantly, provide give full play to bone forming property, enhance osteogenic activity of OCSM, and promote osteogenesis after maxillary sinus floor elevation with new mentality.

上颌窦底提升是解决上颌后牙区骨量不足牙种植的有效方式，但存在提升后窦底空间成骨速度慢、成骨量不足等问题，影响种植体的成功率。上颌窦黏膜骨原细胞(OCSM)具有成骨能力，但其具体的细胞分子作用机制仍不清楚。本课题组前期的体外实验表明犬OCSM可被诱导分化成骨，体内实验证实犬OCSM在上颌窦底提升空间成骨过程中发挥作用，进一步实验发现miR-27参与上颌窦黏膜骨原细胞成骨分化，提示miR-27可能在上颌窦底提升窦底空间成骨中发挥重要作用，本课题组在已有的工作基础上，希望进一步研究确定：①miR-27在OCSM成骨分化过程中作用的靶基因和靶位点；②miR-27在OCSM成骨分化过程发挥作用的细胞信号转导途径。以期明确miR-27发挥成骨作用的机制。通过本课题的研究可为上颌窦底提升充分发挥OCSM的作用、提高OCSM的成骨能力、促进成骨效果提供新的思路和理论基础。

本课题组前期的体外实验表明犬OCSM可被诱导分化成骨，体内实验证实犬OCSM在上颌窦底提升空间成骨过程中发挥作用，进一步实验发现miR-27参与上颌窦黏膜骨原细胞成骨分化，提示miR-27可能在上颌窦底提升窦底空间成骨中发挥重要作用。本课题组在已有的工作基础上，为了进一步研究miR-27调控OCSM成骨分化机制及OCSM分化的关键细胞信号通路，本项目开展以下研究：①miR-27a在犬OCSM成骨分化过程中作用的靶基因和作用机制，结果显示：1. 犬上颌窦底黏膜含有骨原细胞，具有成骨能力；2. miR-27a负向调控犬OCSM成骨分化；3. miR-27a的靶基因是IGF1，IGF1促进OCSM成骨，miR-27a通过靶基因IGF1负向调控OCSM的成骨分化；4. OCSM成骨分化过程中，miR-27a的靶基因IGF1通过经典的Smads蛋白依赖性信号转导通路BMP2-Smad1/5促进成骨，Smads蛋白非依赖性信号转导通路P38MAPK在IGF1介导的促OCSM成骨过程中可能并不发挥作用。②miR-27b-3p在人上颌窦黏膜干细胞成骨分化过程中的作用结果显示：1. 人上颌窦黏膜含有上颌窦黏膜干细胞，具有成骨能力；2. MiR-27b-3p可靶向抑制Sp7表达进而抑制上颌窦黏膜干细胞的成骨分化。本项目阐明了miR-27在上颌窦黏膜骨原细胞成骨分化过程中发挥作用，miR-27参与窦底提升成骨过程及初步明确miR-27调控上颌窦黏膜骨原细胞成骨信号通路的分子机制。因此该项目的顺利完成在为上颌窦底提升充分发挥上颌窦黏膜的作用、促进成骨效果提供新的思路和理论基础，对促进上颌窦底提升的成骨，提高种植体的成功率具有重要的意义。