Inhibition of the terminal differentiation of odontoblasts and their transdifferentiation into osteoblasts in Runx2 transgenic mice

DOI Web Site 被引用文献19件 参考文献63件
  • Miyazaki Toshihiro
    Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
  • Kanatani Naoko
    Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
  • Rokutanda Satoshi
    Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences Department of Oral and Maxillofacial Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences
  • Yoshida Carolina
    Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences
  • Toyosawa Satoru
    Department of Oral Pathology, Osaka University Faculty of Dentistry
  • Nakamura Reiko
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Faculty of Dentistry
  • Takada Shinji
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Faculty of Dentistry
  • Komori Toshihisa
    Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences

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Runx2 is an essential transcription factor for bone and tooth development whose function in odontoblast differentiation remains to be clarified. To pursue this issue, we examined tooth development in Runx2 transgenic mice under the control of Col1a1 promoter (Tg(Col1a1-Runx2) mice). Endogenous Runx2 protein was detected in the nuclei of preodontoblasts, immature odontoblasts, mesenchymal cells in the dental sac, and osteoblasts, while transgene expression was detected in odontoblasts and osteoblasts. Odontoblasts in Tg(Col1a1-Runx2) mice lost their columnar shape and dentin was deposited around the odontoblasts, which were cuboid or flat in shape. The dentin in Tg(Col1a1-Runx2) mice was thin and possessed lacunae that contained odontoblasts and bone canaliculi-like structures, while predentin and dentinal tubules were absent. We examined the expression of dentin matrix protein genes, Col1a1 and dentin sialophosphoprotein (DSPP), by in situ hybridization, and dentin matrix proteins, osteocalcin, osteopontin, and dentin matrix protein 1 (DMP1) as well as an intermediate filament, nestin, by immunohistochemistry to characterize odontoblasts in Tg(Col1a1-Runx2) mice. Results showed Col1a1 expression was down-regulated, DSPP expression was lost, and nestin expression was severely decreased in the odontoblasts of Tg(Col1a1-Runx2) mice. Further, the expressions of osteocalcin, osteopontin, and DMP1 were up-regulated in odontoblasts, although the up-regulation of osteocalcin expression was transient. These findings indicate that Runx2 inhibits the terminal differentiation of odontoblasts, and that Runx2 induces transdifferentiation of odontoblasts into osteoblasts forming a bone structure. Thus, Runx2 expression has to be down-regulated during odontoblast differentiation to acquire full odontoblast differentiation for dentinogenesis.

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