RhoA-YAP/TAZ信号通路对骨缝牵张成骨的分子调控机制研究

Suture Distraction Osteogenesis is commonly used in dental maxillofacial deformity treatment. The curative effect depends on its biological reaction. The interaction between mechanical strain and suture osteogenesis is extremely complex. As one of the most important elements on new bone’s regeneration and reconstruction, the molecular mechanism of suture mesenchymal cell osteogenic differentiation is still unclear. Our research has already found RhoA is involved in suture osteogenesis induced by mechanical strain. However, the downstream signaling molecule of which during the process is still unknown. This research focus on osteogenic differentiation of suture mesemchymal cell under mechanical distraction. We are going to build rat cranial sagittal suture tension model as well as three-dimensional stretching cultured rat cranial sagittal suture mesenchymal cells model. We will use gene silencing system、gene transfection、pathway activator/inhibitor, immunohistochemical staining and kinase activity assay at animal/cell level to explore whether RhoA directly regulates the osteogenic differentiation of suture mesenchymal cell ,or indirectly ,by YAP/TAZ signaling pathways .Our research will further elucidate the regulation effect of RhoA-YAP/TAZ signaling pathways towards distraction osteogenesis. How does new bone appear when the suture is under strain? With an answer at molecular level, we will have the ability to improve the technology as well as curative effect on a theoretical basis.

骨缝牵张成骨技术常用于牙颌面畸形矫治。牵张成骨的生物学反应决定了疗效。机械张力诱导骨缝成骨反应极为复杂，骨缝间充质细胞成骨分化是新骨再生与改建的关键环节之一，其分子机制不清。项目组前期发现RhoA参与机械张力诱导骨缝成骨反应，但在机械张力诱导骨缝成骨过程中，RhoA的下游信号通路尚不明确。本研究聚焦骨缝牵张后成骨中间充质细胞成骨分化，构建大鼠颅骨矢状缝牵张模型和三维牵张培养的大鼠颅骨缝间充质细胞模型，在动物与细胞层次上，采用基因沉默系统、基因转染、信号分子激活剂/抑制剂、免疫组化、激酶活性测定等实验手段，探讨骨缝牵张成骨过程中，RhoA是否调控颅骨缝间充质细胞成骨分化，RhoA是否通过YAP/TAZ信号通路调控颅骨缝牵张骨形成。这将进一步阐明RhoA-YAP/TAZ信号通路对牵张成骨的调控效应，在分子水平上阐明骨缝牵张成骨术中新骨的发生机制，为临床改良该技术并提高疗效提供重要的理论依据。

骨缝牵张成骨技术常用于牙颌面畸形矫治。机械张力诱导骨缝成骨反应极为复杂，骨缝间充质干细胞成骨分化是新骨再生与改建的关键环节之一，其分子机制不清。项目组前期发现RhoA参与机械张力诱导骨缝成骨反应，但在机械张力诱导骨缝成骨过程中，RhoA的下游信号通路尚不明确。本研究聚焦骨缝牵张后成骨中间充质干细胞成骨分化，构建体内颅骨矢状缝牵张模型和三维牵张培养的颅骨缝间充质干细胞模型，在动物与细胞层次上，采用基因沉默系统、信号分子抑制剂、免疫荧光、激酶活性测定等实验手段，发现RhoA通过YAP/TAZ信号通路调控颅骨缝牵张骨形成及机械诱导的颅骨矢状缝干细胞成骨分化。干预该信号通路，颅骨矢状缝牵引成骨受抑制，牵张培养的颅骨矢状缝间充质干细胞成骨向分化受阻碍。本研究在分子水平阐明RhoA-YAP/TAZ信号通路对牵张成骨的调控效应，为临床改良该技术并提高疗效提供重要的理论依据。