Inhibition of the terminal differentiation of odontoblasts and their transdifferentiation into osteoblasts in Runx2 transgenic mice
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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 <I>Col1a1</I> promoter (<I>Tg(Col1a1-Runx2)</I> 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 <I>Tg(Col1a1-Runx2)</I> mice lost their columnar shape and dentin was deposited around the odontoblasts, which were cuboid or flat in shape. The dentin in <I>Tg(Col1a1-Runx2)</I> 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, <I>Col1a1</I> and dentin sialophosphoprotein <I>(DSPP)</I>, by <I>in situ</I> 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 <I>Tg(Col1a1-Runx2)</I> mice. Results showed <I>Col1a1</I> expression was down-regulated, <I>DSPP</I> expression was lost, and nestin expression was severely decreased in the odontoblasts of <I>Tg(Col1a1-Runx2)</I> 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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国際組織細胞学会 | 論文
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