Essential Role of IFT140 in Promoting Dentinogenesis
Essential Role of IFT140 in Promoting Dentinogenesis
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IFT140 在促进牙本质形成中的重要作用
DOI：
10.1177/0022034517741283
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发表时间：
2018-04-01
影响因子：
7.6
通讯作者：
Sun, Y.
中科院分区：
文献类型：
--
作者：
Li, G.;Liu, M.;Sun, Y.
初级纤毛具有高度调控的细胞感觉功能，在组织发育和功能维持中起着关键作用。鞭毛内运输140 （IFT140）是IFT复合体a的一个亚基，专门用于纤毛的逆行运输。Ift140的突变通常与综合征性纤毛病有关，并可能导致孤立的疾病，如视网膜营养不良、短肋和多囊肾。然而，IFT140在牙齿发育中的作用尚未得到很好的研究。本研究揭示了IFT140与牙本质形成的密切关系。在牙齿发育过程中，IFT140在成牙细胞中高度表达。为了进一步了解IFT140在牙本质形成中的作用，我们制作了Ift140flox/flox/Osx-Cre小鼠。Ift140flox/flox/Osx-Cre小鼠牙本质厚度较对照组薄，牙本质形成速度较对照组慢。体外，在成牙细胞中缺失IFT140会导致成牙分化不良，原发纤毛异常，Sonic hedgehog信号分子减少。更重要的是，由于IFT140缺失导致成牙细胞初级纤毛缺失，在牙齿钻孔模型中，修复性牙本质形成受损。这些结果表明纤毛基因IFT140在促进牙本质的形成和修复中是必不可少的。
Primary cilia, with highly regulated cellular sensory functions, play key roles in tissue development and function maintenance. Intraflagellar transport 140 (IFT140) is a subunit of IFT complex A, which is specialized for retrograde transportation in cilia. Mutations of Ift140 are usually associated with syndromic ciliopathy and may cause isolated diseases such as retinal dystrophy, short ribs, and polycystic kidney. However, the role of IFT140 in tooth development has not been well investigated. In this study, a close relationship between IFT140 and dentin formation is disclosed. During tooth development, IFT140 was highly expressed in odontoblasts. To further understand the role of IFT140 in dentinogenesis, Ift140flox/flox/Osx-Cre mouse was generated. The dentin thickness of Ift140flox/flox/Osx-Cre mouse is thinner and the dentin formation is slower than that in control. In vitro, deletion of IFT140 in odontoblasts led to poor odontogenic differentiation, abnormal primary cilia, and decreased Sonic hedgehog signaling molecules. More important, due to loss of primary cilia in odontoblasts by IFT140 deletion, reparative dentin formation was impaired in a tooth-drilling model. These results suggest that cilia gene IFT140 is essential in promoting dentin formation and reparation.