Stim1 Regulates Enamel Mineralization and Ameloblast Modulation

Y. Furukawa, N. Haruyama, M. Nikaido, M. Nakanishi, N. Ryu, M. Oh-Hora, K. Kuremoto, K. Yoshizaki, Y. Takano, I. Takahashi

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16 Citations (Scopus)


Loss-of-function mutations in the Ca2+ release-activated Ca2+ channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 (Stim1 cKO [conditional knockout]), Stim2 (Stim2 cKO), and Stim1 and Stim2 (Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control (Stim1/2fl/fl) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.

Original languageEnglish
Pages (from-to)1422-1429
Number of pages8
JournalJournal of Dental Research
Issue number12
Publication statusPublished - Nov 1 2017

All Science Journal Classification (ASJC) codes

  • Dentistry(all)


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