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<p>The tooth root is a critical component of the tooth anchored to surrounding alveolar bones. Tooth root formation is driven by cells in the apical papilla (AP) that generate new dentin-forming odontoblasts at the root-forming front. Mesenchymal stem cells have been isolated from AP for regenerative use; however, how AP cells physiologically coordinate tooth root formation remains undefined. We find that CXCL12<sup>+</sup> cells emerge in AP under hypoxic environments at the onset of tooth root formation. Using <i>Cxcl12-creER</i>-based cell-lineage analysis, we further find that CXCL12<sup>+</sup> AP cells contribute not only to odontoblasts but also to cementum-forming cementoblasts of the elongating root, while showing plasticity to alveolar bone osteoblasts under regenerative conditions. Canonical Wnt inactivation inhibits odontoblast fates of CXCL12<sup>+</sup> AP cells and induces substantial root truncation, with their aberrant fibroblast fates suppressed by TGF-β receptor inhibitor galunisertib. Therefore, CXCL12<sup>+</sup> AP cells maintain odonto-cementogenic fates in a Wnt-dependent manner, identifying these cells as pivotal dental mesenchymal progenitor cells driving tooth root formation with substantial plasticity.</p>

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Wnt-directed CXCL12-expressing apical papilla progenitor cells drive tooth root formation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Mizuki Nagata,
  • Gaurav T. Gadhvi,
  • Taishi Komori,
  • Yuki Arai,
  • Hiroaki Manabe,
  • Angel Ka Yan Chu,
  • Ramandeep Kaur,
  • Meer Ali,
  • Yuntao Yang,
  • Chiaki Tsutsumi-Arai,
  • Yuta Nakai,
  • Yuki Matsushita,
  • Nicha Tokavanich,
  • W. Jim Zheng,
  • Joshua D. Welch,
  • Noriaki Ono,
  • Wanida Ono

摘要

The tooth root is a critical component of the tooth anchored to surrounding alveolar bones. Tooth root formation is driven by cells in the apical papilla (AP) that generate new dentin-forming odontoblasts at the root-forming front. Mesenchymal stem cells have been isolated from AP for regenerative use; however, how AP cells physiologically coordinate tooth root formation remains undefined. We find that CXCL12+ cells emerge in AP under hypoxic environments at the onset of tooth root formation. Using Cxcl12-creER-based cell-lineage analysis, we further find that CXCL12+ AP cells contribute not only to odontoblasts but also to cementum-forming cementoblasts of the elongating root, while showing plasticity to alveolar bone osteoblasts under regenerative conditions. Canonical Wnt inactivation inhibits odontoblast fates of CXCL12+ AP cells and induces substantial root truncation, with their aberrant fibroblast fates suppressed by TGF-β receptor inhibitor galunisertib. Therefore, CXCL12+ AP cells maintain odonto-cementogenic fates in a Wnt-dependent manner, identifying these cells as pivotal dental mesenchymal progenitor cells driving tooth root formation with substantial plasticity.