Ift88 regulates enamel formation via involving Shh signaling
Ift88 regulates enamel formation via involving Shh signaling
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DOI：
10.1111/odi.14162
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发表时间：
2022-03-01
期刊：
影响因子：
3.8
通讯作者：
Ohazama, Atsushi
中科院分区：
文献类型：
--
作者：
Kudo, Takehisa;Kawasaki, Maiko;Ohazama, Atsushi
目的纤毛疾病是一种广泛的人类疾病，是由初级纤毛功能紊乱引起的。牙釉质异常常见于纤毛病患者;然而，初级纤毛在釉质形成中的作用仍不清楚。材料和方法我们检查了纤毛蛋白Ift 88上皮条件性缺失的小鼠（Ift 88（fl）（/）（fl）; K14 Cre）。结果Ift 88（fl）（/）（fl）; K14 Cre小鼠磨牙早期磨损。一种模式的釉棒，这是在分泌阶段确定的，是混乱的Ift 88突变磨牙。在分泌期表达的釉原蛋白、成釉蛋白、釉蛋白等许多釉发生相关分子在Ift 88突变的磨牙牙胚中表达显著下调。Shh信号是釉质形成所必需的，这被发现在分泌期Ift 88突变磨牙下调。在分泌期应用Shh信号激动剂部分挽救了Ift 88突变小鼠的釉质异常。结论初级纤毛通过Ift 88介导的Shh信号通路在釉质形成的分泌期发挥重要作用。
Objectives The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear. Materials and Methods We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88(fl)(/)(fl);K14Cre). Results Ift88(fl)(/)(fl);K14Cre mice showed premature abrasion in molars. A pattern of enamel rods which is determined at secretory stage, was disorganized in Ift88 mutant molars. Many amelogenesis-related molecules expressing at the secretory stage, including amelogenin and ameloblastin, enamelin, showed significant downregulation in Ift88 mutant molar tooth germs. Shh signaling is essential for amelogenesis, which was found to be downregulated in Ift88 mutant molar at the secretory stage. Application of Shh signaling agonist at the secretory stage partially rescued enamel anomalies in Ift88 mutant mice. Conclusion Findings in the present study indicate that the function of the primary cilia via Ift88 is critical for the secretory stage of amelogenesis through involving Shh signaling.