牙囊和上皮根鞘细胞成无细胞牙骨质的机制

Molecular mechanisms of dental follicle cell and epithelial root sheath cell differentiation into acellular cementum

无细胞牙骨质是锚定牙周纤维和牙根的重要组织结构,牙囊细胞(DFC)通过自身分化和上皮根鞘(ERS)通过上皮-间质转化(EMT)形成的成牙骨质细胞参与无细胞牙骨质形成。牙囊细胞体外移植后可形成纤维样和牙骨质样组织,而牙乳头和上皮根鞘可以诱导牙囊细胞从基因及其蛋白质水平高表达碱性磷酸酶、骨涎蛋白等无细胞牙骨质相关标志物。其中钙离子、骨形态发生蛋白、Wnt/β-连环蛋白通路等目前被认为是介导牙囊细胞成牙骨质分化的信号转导通路。目前发现,调控无机磷酸盐胞内外浓度的转运蛋白对无细胞牙骨质形成调节的敏感性更高。ERS亦可通过EMT形成间质细胞来参与牙周组织的发生。钙结合蛋白D28k、末端较小的同源异形盒-2等在无细胞牙骨质、ERS以及牙囊细胞表达差异都说明了ERS具有成牙骨质细胞特性。在此过程中,TGFβ激活下游蜗牛蛋白后,通过磷脂酰肌醇-3-激酶和蛋白激酶B信号转导通路来介导ERS的无细胞牙骨质分化过程。

Acellular cementum plays an important role in the attachment of the periodontal ligament to the root surface. Many studies worldwide show that cementoblasts that form acellular cementum are derived from the differentiation of dental follicle cells and the epithelial-mesenchymal transition of epithelial root sheath cells. Transplantation of dental follicle cells can differentiate into periodontal fiber-like and cementum-like tissue in vivo. In vitro, both dental papilla cells and epithelial root sheath cells can induce in dental follicle cells the high expression of alkaline phosphatase. Bone sialoprotein serves as the markers of acellular cementum. Bone morphogenetic protein, Ca2＋, and Wnt/β-catenin signaling pathways have also been found in the regulation of dental follicle cell differentiation. Membrane transporters associated with inorganic phosphate have a more sensitive impact on acellular cementum formation. Epithelial root sheath cells can also participate in acellular cementum through epithelial-mesenchymal transition. The differential expression pattern of D28k and distal-less homeobox-2 in dental follicle cells, epithelial root sheath cells, and cementum morphologically indicates that parts of acellular cementum may be derived from epithelial root sheath cells. Moreover, the transformation of growth factor β-snail activates the phosphatidylinositol-3-kinase/protein kinase B signaling pathway involved in the epithelial-mesenchymal transition of epithelial root sheath cells.