Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 2012 Mar 23;287(13):10590-10601. doi: 10.1074/jbc.M111.285874. Epub 2012 Feb 1.
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.
上皮-间充质相互作用调节外胚层器官的生长和形态发生，如牙齿。牙髓干细胞 (DPSCs) 是牙齿间充质的一部分，来源于颅神经嵴，并分化为形成牙本质的成牙本质细胞。然而，DPSCs 与上皮之间的相互作用尚未清楚阐明。在这项研究中，我们建立了一个由富含侧群细胞组成的小鼠牙髓干细胞系 (SP)，该细胞系显示出多能性，可分化为成牙本质细胞、成骨细胞、成脂细胞和神经细胞。我们还分析了 SP 细胞与大鼠牙上皮 SF2 系细胞之间的相互作用。当与 SF2 细胞共培养时，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 调节，受 BMP 拮抗剂 Noggin 抑制。我们还发现，用丝裂霉素 C 处理的 SF2-24 细胞培养的小鼠 iPS 细胞显示出上皮细胞样形态。这些细胞表达上皮细胞标志物 p63 和角蛋白-14，以及成釉细胞标志物釉原蛋白和釉蛋白，而不表达内胚层细胞标志物 Gata6 或中胚层细胞标志物 brachyury。这是首次报道 iPS 细胞通过与牙上皮的相互作用分化为成釉细胞。与牙上皮细胞共培养似乎诱导了有利于成牙本质细胞命运的干细胞分化，这可能是牙齿生物工程策略的一种有用方法。
