Stem Cell Regulatory Gene Expression in Human Adult Dental Pulp and Periodontal Ligament Cells Undergoing Odontogenic/Osteogenic Differentiation

Stem Cell Regulatory Gene Expression in Human Adult Dental Pulp and Periodontal Ligament Cells Undergoing Odontogenic/Osteogenic Differentiation
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成人牙髓和牙周膜细胞中牙源/成骨分化的干细胞调节基因表达

DOI:
10.1016/j.joen.2009.07.005
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发表时间:
2009-10-01
影响因子:
4.2
通讯作者:
Xiao, Yin
Xiao, Yin
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Lu;Ling, Junqi;Xiao, Yin

文献摘要

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简介:在发育和再生过程中,牙生成和成骨是由几个主调控基因驱动的一系列信号启动的。方法:在本研究中,我们研究了牙髓细胞(DPC)和牙周膜细胞(PDLC)中84个干细胞相关基因在成牙/成骨分化过程中的差异表达。结果:我们的结果表明,尽管存在相当大的重叠,但某些基因在 PDLC 中比在 DPC 中具有更多的差异表达。 CCND2、DLL1 和 MME 是 PDLC 和 DPC 中主要上调的基因,而 KRT15 是 PDLC 和 DPC 中唯一在牙源分化和成骨分化中显着下调的基因。有趣的是,牙源性和成骨性分化中的大量调控基因通过Notch、Writ、转化生长因子β(TGF-β)/骨形态发生蛋白(BMP)和钙粘蛋白信号通路相互作用或串扰,例如APC、DLL1、CCND2、BMP2和CDH1的调控。使用大鼠牙髓和牙周缺损模型,验证了 BMP2 和 CDH1 在牙髓和牙周组织再生中的空间定位的表达和分布。结论:本研究概述了牙源性/成骨分化过程中 DPC 和 PDLC 中干细胞相关基因的表达,并揭示这些基因可能通过 Notch、Wnt、TGF-β/BMP 和钙粘蛋白信号通路相互作用,在决定牙源性细胞和牙组织再生的命运中发挥关键作用。这些发现为牙组织矿化和再生的分子机制提供了新的见解。 (J Endod 2009;35:1368-1376)
Introduction: During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. Methods: In this study, we investigated the differential expression of 84 stem cell-related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Results: Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Writ, transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. Conclusions: This study has generated an overview of stem cell-related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-beta/BMP, and cadherin signaling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration. (J Endod 2009;35:1368-1376)