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Notch信号在扮演发育和细胞命运决定中起重要作用。Notch受体和配体在发育期牙源性上皮和间充质中的表达说明该信号可能参与调节牙齿器官发生。出生后人牙髓干细胞(DPSCs)具有间充质干细胞的特性且能分化为成牙本质细胞。此实验为研究Notch信号是否参与DPSCs的成牙本质细胞分化。Notch配体Jagged-1的过表达能激活DPSCs的Notch信号通路,在体外抑制成牙本质细胞谱系分化。体内环境中表达Jagged-1的DPSCs不能形成矿化组织。组成性激活的Notch1胞内段(Notch-ICD)的过表达也抑制了DPSCs的成牙本质细胞向分化。综上,本研究证明notch信号能抑制人DPSCs向成牙本质细胞的分化。
J Dent Res. 2008 Mar;87(3):250-5. Inhibition of human dental pulp stem cell differentiation by notch signaling.
Zhang C, Chang J, Sonoyama W, Shi S, Wang CY.
Department of Special Dental Service, School and Hospital of Stomatology, Peking University, Beijing, China;
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.
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