IFT80调控上颌快速扩大腭中缝骨改建的机制研究

我们前期研究发现初级纤毛-多囊蛋白复合物在上颌快速扩大机械生物信号转导中发挥重要作用。细胞纤毛内转运蛋白（IFT Protein）是初级纤毛形成与维持的关键。为明确细胞纤毛内转运蛋白80（IFT80）在上颌快速扩大腭中缝骨改建中的调控机制，本项目利用小鼠上颌快速扩大动物模型，研究IFT80以及机械生物信号转导相关调控因子的时空表达规律；利用RNA干扰技术沉默小鼠成骨细胞IFT80基因，同时构建体外牵张培养成骨细胞模型，研究IFT80对体外牵张培养成骨细胞的增殖、分化以及初级纤毛形成和机械生物信号转导的调控机制；利用成骨细胞与破骨细胞共培养模型，研究IFT80基因沉默对体外牵张培养的成骨细胞调节破骨细胞功能的影响；最后进行在体转染实验，研究体内IFT80基因沉默对腭中缝牵张骨形成的影响。本研究探索了促进骨缝牵张骨形成钙化和减少骨吸收的机制，为发展更有效扩大腭中缝的方法奠定理论基础。

Rapid maxillary expansion is a preferred treatment to maxillary transverse skeletal deficiency in orthodontics. However, the patients after surgery still have a risk of recurrence, even after a retention phase. Our previous study demonstrated that the polycystin-primary cilia complex plays a key role in regulating rapid maxillary expansion mechanotransduction. Intraflagellar transport (IFT) proteins are known to be essential for primary cilia formation. The aim of this study is to investigate the role of IFT Protein 80 in bio-mechanical bone remodeling during rapid maxillary expansion. Using the murine midpalatal suture expansion model, we will examine the spatiotemporal expressions of IFT80 and mechanotransduction-related factors in vivo. At the molecular level, we will study the mechanisms in which IFT80 regulates osteoblast proliferation and differentiation, primary cilia formation and mechanotransduction under bio-mechanical strain by silencing IFT80 with lentivirus-mediated shRNA technology. We will further investigate the role of IFT80 in osteoblast, which were subjected to mechanical strain, in regulating osteoclast differentiation and bone resportion in a transwell co-culture system. Finally, we will study the role of IFT80 in rapid maxillary expansion osteogenesis in vivo by injecting the lentivirus-mediated shRNA vector into midpalatal suture regions. Our study explored the mechanisms that promote the new bone formation and reduce the new bone resorption in rapid maxillary expansion, and provide the theoretical evidences to improve rapid maxillary expansion for treatment of maxillary transverse skeletal deficiency.