Significance of Smad4-Osx signaling in odontoblast differentiation
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Dentin is formed by odontoblasts that have differentiated from dental mesenchymal cells. Research indicates that Smad4-mediated Wnt signaling plays a crucial role in the fate of dental mesenchymal cells, and that Osx is essential for osteoblast differentiation. To understand the molecular mechanisms that control odontoblast differentiation and dentin formation, we investigated the functional significance of Smad4 and Osx in the regulation of odontoblast differentiation through tissue-specific inactivation of Smad4 and Osx in osteocalcin-Cre (OC-Cre)-expressing cells. Simultaneous ablation of Smad4 and Osx results in more severe defects in odontoblast differentiation and dentin formation compared to single-gene-disrupted mice. In OC-Cre;Smad4fl/fl:Osxfl/fl mice, crown dentin was extremely thin and was accompanied by loss of polarity in odontoblasts. Furthermore, a lack of molar roots was caused by severe impairment of root odontoblast differentiation. Although Hertwig’s epithelial root sheath (HERS) was extended apically after crown formation, root odontoblast differentiation was disrupted. Immunohistochemistry analysis revealed that Lef-1, a Wnt target protein, and Ki67, a cell proliferation marker, demonstrated increased immunoreactivity in the dental papilla adjacent to HERS in OC-Cre;Smad-4fl/fl:Osxfl/fl mice. These results indicate that simultaneous disruption of Smad4 and Osx leads to increased cell proliferation through upregulation of Wnt activity and impaired odontoblast differentiation. Thus, Smad4 and Osx are essential for maintaining odontogenic fate in dental mesenchyme and odontoblast differentiation, respectively. Furthermore, the Wnt-Smad4-Osx signaling axis is required for proliferation, odontoblast differentiation, and dentin formation during tooth development.
Abstract
Dentin is formed by odontoblasts that have differentiated from dental mesenchymal cells. Research indicates that Smad4-mediated Wnt signaling plays a crucial role in the fate of dental mesenchymal cells, and that Osx is essential for osteoblast differentiation. To understand the molecular mechanisms that control odontoblast differentiation and dentin formation, we investigated the functional significance of Smad4 and Osx in the regulation of odontoblast differentiation through tissue-specific inactivation of Smad4 and Osx in osteocalcin-Cre (OC-Cre)-expressing cells. Simultaneous ablation of Smad4 and Osx results in more severe defects in odontoblast differentiation and dentin formation compared to single-gene-disrupted mice. In OC-Cre;Smad4fl/fl:Osxfl/fl mice, crown dentin was extremely thin and was accompanied by loss of polarity in odontoblasts. Furthermore, a lack of molar roots was caused by severe impairment of root odontoblast differentiation. Although Hertwig’s epithelial root sheath (HERS) was extended apically after crown formation, root odontoblast differentiation was disrupted. Immunohistochemistry analysis revealed that Lef-1, a Wnt target protein, and Ki67, a cell proliferation marker, demonstrated increased immunoreactivity in the dental papilla adjacent to HERS in OC-Cre;Smad-4fl/fl:Osxfl/fl mice. These results indicate that simultaneous disruption of Smad4 and Osx leads to increased cell proliferation through upregulation of Wnt activity and impaired odontoblast differentiation. Thus, Smad4 and Osx are essential for maintaining odontogenic fate in dental mesenchyme and odontoblast differentiation, respectively. Furthermore, the Wnt-Smad4-Osx signaling axis is required for proliferation, odontoblast differentiation, and dentin formation during tooth development.
참고문헌 (26)
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