牙本质矿化不良缺乏有效治疗方法，因此研究牙本质矿化及调控具有重要意义。已知成牙本质细胞的极性建立是牙本质矿化的必要条件。我们发现在小鼠牙乳头细胞中特异性敲除BMP受体Acvr1后，小鼠牙本质矿化不良，成牙本质细胞极性消失，Rho GTP酶分子表达下调。由于Rho GTP酶是调控细胞不对称分布的关键信号分子，因此推测ACVR1通过Rho GTP酶信号调控成牙本质细胞极化进而影响牙本质矿化。本项目采用影像学、组织学、细胞和分子生物学方法，研究ACVR1对牙本质矿化和成牙本质细胞极化的影响；通过基因沉默和过表达，探讨Rho GTP酶信号对成牙本质细胞极化的作用，筛选关键的Rho GTP酶分子；进一步结合牙胚重组和肾被膜下移植技术，明确Acvr1敲除小鼠中，Rho GTP酶信号对成牙本质细胞极化和牙本质矿化的影响，阐明ACVR1在牙本质矿化中的作用及分子机理，为促进牙本质矿化和牙本质再生奠定基础。

Defects of dentin mineralization are commonly seen in clinic, however, there is no effective therapy, thus it is of great significance to explore the regulation of dentin mineralization. It is known that the establishment of polarity in odontoblasts is necessary for dentin mineralization. In our preliminary data, we found that specific disruption of Acvr1 (one of the type I BMP receptors) in dental mesenchyme led to a decrease in dentin mineralization, as well as the disappearance of odontoblast polarity and down-regulation of Rho GTPases in mice. It is reported that Rho GTPases are the key regulators in the asymmetric organizations of cells. We hypothesized that ACVR1 regulates the polarization of odontoblasts via Rho GTPase signaling, thus affects dentin mineralization. In this project, we will examine the effects of ACVR1 on the mineralization of dentin, and the polarization of odontoblasts by micro-CT, histology, cellular and molecular biology, using Acvr1 conditional knockout mouse model. We will explore the effects of Rho GTPase signaling on odontoblast polarization, and determine the key molecule in Rho GTPases, using the technology of gene silencing and overexpression. Further, we will confirm the effects of the Rho GTPase molecule on the polarization of odontoblasts and the mineralization of dentin in Acvr1 conditional knockout mice, using tooth germ recombination and kidney capsule transplantation. We will elucidate the effects and the molecular mechanisms of ACVR1 on dentin mineralization. Our study will lay a foundation for the mineralization and regeneration of dentin.