不同信号通路对牙周膜干细胞成骨分化的影响

Effects of different signaling pathways on osteogenic differentiation of periodontal ligament stem cells

背景:牙周膜干细胞作为牙源性间充质干细胞的一种,具有成骨分化潜能,可应用于牙周组织再生修复,而牙周膜干细胞的成骨分化涉及多种信号通路的调控。目的:综述目前已研究因子介导的与牙周膜干细胞成骨分化相关的信号通路及其对成骨分化的影响。方法:在PubMed和中国知网数据库,设置检索时间为2010-2022年,总结了2010年以来与牙周膜干细胞成骨分化相关的8个信号通路的研究进展,最终纳入60篇文献进行分析讨论。结果与结论:(1)牙周膜干细胞作为牙源性间充质干细胞,具有良好的增殖、自我更新及多向分化潜能的特点;作为牙周组织再生修复的种子细胞,牙周膜干细胞应用于牙周炎的治疗具有广阔的前景。(2)目前已有大量研究证实各类因子与牙周膜干细胞成骨分化之间的潜在关系是通过介导各信号通路产生,虽然各信号通路在促进牙周膜干细胞成骨分化方面均有一定作用,但研究最多的是MAPK信号通路和Wnt信号通路。(3)MAPK信号通路包括4条途径,广泛存在于细胞中,对于调节细胞的增殖及分化发挥着重要作用;经典的Wnt/β-连环蛋白通路是控制骨稳态的最重要信号通路之一,已有大量研究证实其与牙周膜干细胞成骨分化存在相关性。(4)目前大多数研究仅通过体外矿化实验证实了某些因子可以激活MAPK信号通路和经典的Wnt/β-连环蛋白通路,提高矿化基因的表达,进而促进牙周膜干细胞成骨分化,但对于这些通路如何被激活,以及该通路影响牙周膜干细胞成骨分化的具体机制还有待进一步研究。(5)不同研究因子介导的各类信号通路的激活或抑制显著地影响了牙周膜干细胞的成骨分化;了解牙周膜干细胞成骨分化相关信号通路,将有利于牙周膜干细胞应用于牙周组织再生,从而有效减少因牙周炎而导致的牙齿脱落。

BACKGROUND:Periodontal membrane stem cells,as a kind of odontogenic mesenchymal stem cells,have osteogenic differentiation potential and can be applied to periodontal tissue regeneration and repair,while the osteogenic differentiation of periodontal membrane stem cells involves the regulation of multiple signaling pathways.OBJECTIVE:To review the factor-mediated signaling pathways associated with osteogenic differentiation of periodontal membrane stem cells and their effects on osteogenic differentiation.METHODS:In PubMed and CNKI,the search time was set from 2010 to 2022.The research progress of eight major signaling pathways associated with osteogenic differentiation of periodontal ligament stem cells since 2010 was summarized.Finally,60 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Periodontal membrane stem cells,as odontogenic mesenchymal stem cells,have the characteristics of good proliferation,selfrenewal and multidirectional differentiation potential.As seed cells for periodontal tissue regeneration and restoration,periodontal membrane stem cells have broad prospects for the treatment of periodontitis.(2)At present,a large number of studies have confirmed that the potential relationship between various factors and periodontal membrane stem cell osteogenic differentiation is generated by mediating each signaling pathway.Although each signaling pathway has a certain role in promoting the osteogenic differentiation of periodontal membrane stem cells,the most studied is the MAPK signaling pathway and the Wnt signaling pathway.(3)The MAPK signaling pathway includes four pathways,which are widely present in cells and play an important role in regulating cell proliferation and differentiation.The classic Wnt/β-catenin pathway is one of the most important signaling pathways for controlling bone homeostasis,and numerous studies have confirmed its association with osteogenic differentiation of periodontal membrane stem cells.(4)At present,most of the current research has only confirmed through in vitro mineralization experiments that certain factors can activate the MAPK signaling pathway and the classic Wnt/β-catenin pathway,improve the expression of mineralization genes,and thus promote the osteogenic differentiation of periodontal membrane stem cells,but further research is needed on how these pathways are activated and the specific mechanisms of this pathway affecting the osteogenic differentiation of periodontal membrane stem cells.(5)The activation or inhibition of various signaling pathways mediated by different research factors significantly affected the osteogenic differentiation of periodontal membrane stem cells.Understanding the signaling pathways associated with osteogenic differentiation of periodontal membrane stem cells will facilitate the application of periodontal membrane stem cells to periodontal tissue regeneration,thereby effectively reducing tooth loss due to periodontitis.