细胞自噬在正畸牵张力诱导间充质干细胞成骨向分化过程中的作用研究

Tooth movement is the core of orthodontics. The osteogenesis of tension side under orthodontic force has great significance on tooth movement and stability, which involves complex mechanical and biological signal transduction, and the mechanism has not yet fully elucidated. Studies have found that the cell’s cytoskeleton change by the tension can cause cell’s autophagy enhanced. But whether the autophagy play a role on the distraction osteogenesis of orthodontic tooth movement, has not been reported. We found that in the early stage of rat orthodontic force model, the expression of autophagy-related protein and osteogenesis-related factor in the tension-side periodontal tissue was increased. On the basis of previous work, we will investigate whether cell autophagy was involved in the osteogenesis differentiation of mesenchymal stem cells induced by orthodontic tension through animal experiments and in vitro studies. Through cell gene silencing and conditional gene knockout mice, analysis the role and mechanism of cell autophagy. Furthermore, explore whether it can promote distraction osteogenesis by modulating autophagy. This study is expected to further elucidate the mechanism of osteogenesis under tension, which provides a new idea for orthodontic treatment to promote periodontal tissue remodeling and accelerate tooth movement.

口腔正畸的核心是牙齿的移动。牙齿受到正畸力后，张力侧的成骨作用对牙齿的移动和稳定意义重大，其中涉及复杂的机械与生物信号的转导，机制至今仍未能完全阐明。研究发现细胞受到牵张力后，细胞骨架发生改变，可以引起细胞的自噬作用增强。但细胞自噬是否在正畸牙齿移动、牵张成骨中发挥作用，至今未见报道。课题组前期在大鼠正畸加力模型中发现，张力侧牙周组织受力早期自噬相关蛋白及成骨相关因子表达增强。本课题拟在前期工作的基础上，通过动物实验和体外研究，观察细胞自噬是否参与了牵张力诱导的间充质干细胞成骨向分化，通过细胞基因沉默技术和条件性基因敲除小鼠分析细胞自噬在其中的作用及机制，并进一步探讨通过药物调节细胞自噬作用，是否可以促进牵张成骨。本研究有望进一步阐明牵张力作用下的成骨机制，为正畸临床促进牙周组织改建、加速牙齿移动提供新的思路。

口腔正畸的核心是牙齿的移动。牙齿受到正畸力后，张力侧的成骨作用对牙齿的移动和稳定意义重大，其中涉及复杂的机械与生物信号的转导，机制至今仍未能完全阐明。本课题通过动物实验和体外细胞研究，观察细胞自噬在牵张力诱导间充质干细胞成骨向分化过程中的表达，发现细胞自噬相关因子与成骨相关因子的变化趋势基本相同，可见细胞自噬参与了牵张力诱导的间充质干细胞成骨向分化的过程；通过细胞基因沉默技术，在自噬相关基因ATG7沉默细胞的研究中发现，当自噬表达水平被明显抑制时，成骨相关因子的表达水平也会出现相应的降低；通过药物调节发现，自噬水平的提高能够有效促进成骨向分化，而降低细胞自噬的水平在一定程度上则抑制了这一过程。综上研究结果证实，在正畸牵张力诱导间充质干细胞成骨向分化过程中，细胞自噬发挥了重要的作用，调节细胞自噬作用可以促进正畸张力侧成骨，为临床促进牙周组织改进、加速牙齿移动提供了新的思路。