Faculty, Staff and Student Publications
Language
English
Publication Date
7-1-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-61048-x
PMID
40595672
PMCID
PMC12216879
PubMedCentral® Posted Date
7-1-2025
PubMedCentral® Full Text Version
Post-print
Abstract
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.
Keywords
Chemokine CXCL12, Animals, Tooth Root, Mice, Mesenchymal Stem Cells, Wnt Signaling Pathway, Dental Papilla, Odontogenesis, Stem Cells, Dental Cementum, Cell Differentiation, Cell Lineage, Wnt Proteins
Published Open-Access
yes
Recommended Citation
Nagata, Mizuki; Gadhvi, Gaurav T; Komori, Taishi; et al., "Wnt-Directed CXCL12-Expressing Apical Papilla Progenitor Cells Drive Tooth Root Formation" (2025). Faculty, Staff and Student Publications. 682.
https://digitalcommons.library.tmc.edu/uthshis_docs/682