Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis.
Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis.
复制标题
胰岛素样生长因子 1 调节生物工程牙齿形态发生。
DOI：
10.1038/s41598-018-36863-6
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Takano-Yamamoto T
中科院分区：
文献类型：
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作者：
Oyanagi T;Takeshita N;Hara M;Ikeda E;Chida T;Seki D;Yoshida M;Seiryu M;Takano I;Kimura S;Oshima M;Tsuji T;Takano-Yamamoto T
再生治疗，以取代缺牙是一个关键的研究领域。利用小鼠牙胚细胞，通过器官胚法制备了功能性生物工程牙齿。然而，与天然牙齿相比，这些生物工程牙齿的尺寸明显较小，并且表现出异常的牙冠形状。正确的牙齿大小和形状有助于它们的正常功能。因此，需要一种方法来控制生物工程牙齿的形态。在这里，我们研究了胰岛素样生长因子1（IGF1）是否可以调节生物工程牙齿的大小和形状，并评估了这种调节的潜在机制。IGF1治疗显著增加了生物工程牙胚的大小，同时保持了正常的牙齿组织学。IGF1处理的生物工程牙齿是由肾包膜下和颌骨中的生物工程牙胚发育而来的，显示出尺寸和牙尖数量的增加。IGF1增加了生物工程牙胚中表达成纤维细胞生长因子（Fgf4）的釉质结的数量，并促进了牙上皮细胞和间充质细胞的增殖和分化。这项研究首次揭示了IGF 1通过诱导釉质结形成以及牙上皮细胞和间充质细胞的增殖和分化来增加生物工程牙齿的大小和牙尖数量。
Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number offibroblast growth factor(Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.