Interaction between fibronectin and β1 integrin is essential for tooth development.
Interaction between fibronectin and β1 integrin is essential for tooth development.
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DOI：
10.1371/journal.pone.0121667
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fukumoto S
中科院分区：
文献类型：
--
作者：
Saito K;Fukumoto E;Yamada A;Yuasa K;Yoshizaki K;Iwamoto T;Saito M;Nakamura T;Fukumoto S
牙上皮和细胞外基质相互作用，以确保细胞生长和分化导致形成适当大小和质量的牙齿。为了确定纤维连接蛋白在牙上皮分化和牙齿形成中的作用，我们分析了其在发育中的切牙中的表达。纤维连接蛋白mRNA在牙胚上皮的分泌前期表达，在分泌期和成熟早期表达减少，在成熟晚期表达增加。来自出生后第1天磨牙的牙上皮细胞与纤连蛋白包被的培养皿的结合被RGD肽抑制，但不被RAD肽抑制，并且被β1整合素中和抗体抑制，这表明纤连蛋白-β1整合素相互作用有助于牙上皮细胞结合。由于纤维连接蛋白和β1整合素在牙间充质中高度表达，因此很难精确确定它们的相互作用如何影响体内牙上皮分化。因此，我们分析了β1整合素条件性基因敲除小鼠（Intβ 1 lox-/lox-/K14-Cre），发现它们表现出部分釉质发育不全，磨牙萌出延迟，成釉细胞分化延迟，但成牙本质细胞未分化。此外，在成釉细胞成熟后期观察到囊样结构。敲除小鼠的牙上皮细胞不与纤连蛋白结合，并且神经营养因子-4诱导这些细胞中成釉蛋白表达被RGD肽或纤连蛋白siRNA抑制，表明纤连蛋白和β1整合素之间的上皮相互作用对于成釉细胞分化和釉质形成是重要的。
The dental epithelium and extracellular matrix interact to ensure that cell growth and differentiation lead to the formation of teeth of appropriate size and quality. To determine the role of fibronectin in differentiation of the dental epithelium and tooth formation, we analyzed its expression in developing incisors. Fibronectin mRNA was expressed during the presecretory stage in developing dental epithelium, decreased in the secretory and early maturation stages, and then reappeared during the late maturation stage. The binding of dental epithelial cells derived from postnatal day-1 molars to a fibronectin-coated dish was inhibited by the RGD but not RAD peptide, and by a β1 integrin-neutralizing antibody, suggesting that fibronectin-β1 integrin interactions contribute to dental epithelial-cell binding. Because fibronectin and β1 integrin are highly expressed in the dental mesenchyme, it is difficult to determine precisely how their interactions influence dental epithelial differentiation in vivo. Therefore, we analyzed β1 integrin conditional knockout mice (Intβ1lox-/lox-/K14-Cre) and found that they exhibited partial enamel hypoplasia, and delayed eruption of molars and differentiation of ameloblasts, but not of odontoblasts. Furthermore, a cyst-like structure was observed during late ameloblast maturation. Dental epithelial cells from knockout mice did not bind to fibronectin, and induction of ameloblastin expression in these cells by neurotrophic factor-4 was inhibited by treatment with RGD peptide or a fibronectin siRNA, suggesting that the epithelial interaction between fibronectin and β1 integrin is important for ameloblast differentiation and enamel formation.
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