Liu Lu, Ling Junqi, Wei Xi, Wu Liping, Xiao Yin
Department of Operative Dentistry, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Endod. 2009 Oct;35(10):1368-76. doi: 10.1016/j.joen.2009.07.005. Epub 2009 Aug 28.
During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes.
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.
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, Wnt, 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.
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.
在发育和再生过程中,牙发生和成骨由几个主要调控基因驱动的一系列信号启动。
在本研究中,我们调查了84个干细胞相关基因在经历牙源性/成骨性分化的牙髓细胞(DPCs)和牙周膜细胞(PDLCs)中的差异表达。
我们的结果表明,尽管存在相当大的重叠,但某些基因在PDLCs中的差异表达比在DPCs中更多。CCND2、DLL1和MME是PDLCs和DPCs中主要上调的基因,而KRT15是在牙源性和成骨性分化中在PDLCs和DPCs中均显著下调的唯一基因。有趣的是,牙源性和成骨性分化中的大量调控基因通过Notch、Wnt、转化生长因子β(TGF-β)/骨形态发生蛋白(BMP)和钙黏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,已验证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。
本研究概述了牙源性/成骨性分化过程中DPCs和PDLCs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和钙黏蛋白信号通路相互作用,在决定牙源性细胞命运和牙组织再生中起关键作用。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。