Role of Epithelial-Stem Cell Interactions during Dental Cell Differentiation
Role of Epithelial-Stem Cell Interactions during Dental Cell Differentiation
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DOI：
10.1074/jbc.m111.285874
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发表时间：
2012-03-23
影响因子：
4.8
通讯作者：
Fukumoto, Satoshi
中科院分区：
文献类型：
--
作者：
Arakaki, Makiko;Ishikawa, Masaki;Fukumoto, Satoshi
上皮-间充质相互作用调节外胚层器官如牙齿的生长和形态发生。牙髓干细胞(DPSCs)是牙本质间充质的一部分，来源于颅神经脊，分化为牙本质形成成牙本质细胞。然而，DPSCs与上皮细胞之间的相互作用尚不清楚。在这项研究中，我们建立了一种小鼠牙髓干细胞系(SP)，它由丰富的侧群细胞组成，显示出向成牙、成骨、成脂和神经源性细胞分化的多潜能。我们还分析了SP细胞与大鼠牙上皮SF2细胞之间的相互作用。当与SF2细胞共同培养时，SP细胞分化为表达牙本质涎磷蛋白的成牙本质细胞。这种分化受BMP2和BMP4的调节，并被BMP拮抗剂Noggin抑制。我们还发现，与丝裂霉素C处理的SF2-24细胞一起培养的小鼠iPS细胞呈现上皮样细胞的形态。这些细胞表达上皮细胞标记p63和细胞角蛋白14，成釉细胞标记成釉蛋白和成釉蛋白，而不表达内胚层细胞标记GATA6或中胚层细胞标记brachyury。这是iPS细胞通过与牙齿上皮相互作用而分化为成釉细胞的首次报道。与牙齿上皮细胞共培养似乎可以诱导干细胞分化，有利于牙源性细胞的命运，这可能是一种有用的牙齿生物工程策略。
Epithelial-mesenchymal interactions regulate the growth and morphogenesis of ectodermal organs such as teeth. Dental pulp stem cells (DPSCs) are a part of dental mesenchyme, derived from the cranial neural crest, and differentiate into dentin forming odontoblasts. However, the interactions between DPSCs and epithelium have not been clearly elucidated. In this study, we established a mouse dental pulp stem cell line (SP) comprised of enriched side population cells that displayed a multipotent capacity to differentiate into odontogenic, osteogenic, adipogenic, and neurogenic cells. We also analyzed the interactions between SP cells and cells from the rat dental epithelial SF2 line. When cultured with SF2 cells, SP cells differentiated into odontoblasts that expressed dentin sialophosphoprotein. This differentiation was regulated by BMP2 and BMP4, and inhibited by the BMP antagonist Noggin. We also found that mouse iPS cells cultured with mitomycin C-treated SF2-24 cells displayed an epithelial cell-like morphology. Those cells expressed the epithelial cell markers p63 and cytokeratin-14, and the ameloblast markers ameloblastin and enamelin, whereas they did not express the endodermal cell marker Gata6 or mesodermal cell marker brachyury. This is the first report of differentiation of iPS cells into ameloblasts via interactions with dental epithelium. Co-culturing with dental epithelial cells appears to induce stem cell differentiation that favors an odontogenic cell fate, which may be a useful approach for tooth bioengineering strategies.