Zhang C, Chang J, Sonoyama W, Shi S, Wang C-Y
Department of Special Dental Service, School and Hospital of Stomatology, Peking University, Beijing, China.
J Dent Res. 2008 Mar;87(3):250-5. doi: 10.1177/154405910808700312.
Notch signaling plays a critical role in development and cell fate specification. Notch receptors and ligands have been found to be expressed in dental epithelium or mesenchyme in the developing tooth, suggesting that Notch signaling may regulate odontogenesis. Post-natal human dental pulp stem cells (DPSCs) isolated from the dental pulp have characteristics of mesenchymal stem cells and can differentiate into odontoblasts. In this study, we examined whether Notch signaling regulated the odontoblastic differentiation of DPSCs. We found that over-expression of the Notch ligand, Jagged-1, activated the Notch signaling pathway in DPSCs. Jagged-1 inhibited the odontoblastic differentiation of DPSCs in vitro. Jagged-1-expressing DPSCs could not form mineralized tissues in vivo. Moreover, over-expression of the constitutively activated Notch1 intracellular domain (Notch-ICD) also inhibited odontoblastic differentiation of DPSCs. Taken together, our results demonstrate that Notch signaling can inhibit the odontoblastic differentiation of DPSCs.
Notch信号通路在发育和细胞命运决定中起着关键作用。已发现Notch受体和配体在发育中的牙齿的牙上皮或间充质中表达，这表明Notch信号通路可能调节牙胚发生。从牙髓中分离出的出生后人类牙髓干细胞（DPSCs）具有间充质干细胞的特征，并且可以分化为成牙本质细胞。在本研究中，我们检测了Notch信号通路是否调节DPSCs的成牙本质细胞分化。我们发现Notch配体Jagged-1的过表达激活了DPSCs中的Notch信号通路。Jagged-1在体外抑制了DPSCs的成牙本质细胞分化。表达Jagged-1的DPSCs在体内不能形成矿化组织。此外，组成型激活的Notch1胞内结构域（Notch-ICD）的过表达也抑制了DPSCs的成牙本质细胞分化。综上所述，我们的结果表明Notch信号通路可以抑制DPSCs的成牙本质细胞分化。
