Dentin phosphophoryn in the matrix activates AKT and mTOR signaling pathway to promote preodontoblast survival and differentiation.
Dentin phosphophoryn in the matrix activates AKT and mTOR signaling pathway to promote preodontoblast survival and differentiation.
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基质中的牙本质磷酸化激活AKT和MTOR信号传导途径，以促进前牙本质细胞存活和分化。
DOI：
10.3389/fphys.2015.00221
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发表时间：
2015
影响因子：
4
通讯作者：
George A
中科院分区：
文献类型：
--
作者：
Eapen A;George A
牙本质磷酸蛋白（DPP）是由成牙本质细胞合成的细胞外基质蛋白。它是高度酸性的，磷酸化的蛋白质对钙离子具有很强的亲和力。因此，细胞外基质中的DPP可以促进羟基磷灰石成核，并可以调节生长晶体的大小。除了其钙结合特性外，DPP还可以启动ECM（细胞外基质）的信号传导功能。促进前成牙本质细胞分化为功能完整的成牙本质细胞的信号尚不清楚。在这项研究中，我们证明，前成牙本质细胞的DPP矩阵，产生机械和生化信号。这是由整合素与含有DPP的RGD的连接引发的。观察到的下游生化反应是AKT（蛋白激酶B）和mTOR（雷帕霉素的哺乳动物靶标）信号传导通路的激活，导致转录因子NF-κB（核因子κB）的激活。终末分化的前成牙本质细胞进行了评估，通过识别磷酸盐和钙沉积在基质中使用von Kossa和茜素红染色分别。识别DPP在牙本质基质中启动的信号通路将有助于设计牙本质组织工程的策略。
Dentin phosphophoryn (DPP) is an extracellular matrix protein synthesized by odontoblasts. It is highly acidic and the phosphorylated protein possesses a strong affinity for calcium ions. Therefore, DPP in the extracellular matrix can promote hydroxyapatite nucleation and can regulate the size of the growing crystal. Besides its calcium binding property, DPP can initiate signaling functions from the ECM (Extracellular matrix). The signals that promote the cytodifferentiation of preodontoblasts to fully functional odontoblasts are not known. In this study, we demonstrate that preodontoblasts on a DPP matrix, generates mechanical and biochemical signals. This is initiated by the ligation of the integrins with the RGD containing DPP. The downstream biochemical response observed is the activation of the AKT(protein kinase B) and mTOR (mammalian target of rapamycin) signaling pathways leading to the activation of the transcription factor NF-κB (Nuclear factor κB). Terminal differentiation of the preodontoblasts was assessed by identifying phosphate and calcium deposits in the matrix using von Kossa and Alizarin red staining respectively. Identifying the signaling pathways initiated by DPP in the dentin matrix would help in devising strategies for dentin tissue engineering.