Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb−/−Runx2+/− Murine Incisors

Kazuyuki Saito, Katsu Takahashi, Boyen Huang, Masakazu Asahara, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Sayaka Mishima, Masaki Nagata, Machiko Iida, Yoshihito Tokita, Masato Asai, Akira Shimizu, Toshihisa Komori, Hidemitsu Harada, Mary MacDougall, Manabu Sugai, Kazuhisa Bessho

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Abstract

Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. Cebpb and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. Cebpb and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.
Original languageEnglish
Article number5169
Pages (from-to)1-13
Number of pages13
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 26 Mar 2018

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    Saito, K., Takahashi, K., Huang, B., Asahara, M., Kiso, H., Togo, Y., Tsukamoto, H., Mishima, S., Nagata, M., Iida, M., Tokita, Y., Asai, M., Shimizu, A., Komori, T., Harada, H., MacDougall, M., Sugai, M., & Bessho, K. (2018). Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb−/−Runx2+/− Murine Incisors. Scientific Reports, 8(1), 1-13. [5169]. https://www.nature.com/articles/s41598-018-23515-y