Characterizing CXCL12+ Apical Mesenchymal Cells as Root-forming Progenitor Cells

Pulp regeneration is dependent on infection control, biomaterials, stem cells and signaling molecules. SCAPs differentiate at a higher proliferation rate than DPSCs and express important chemokines such as CXCL12. The first aim of our study defined the role of CXCL12⁺ apical mesenchymal cells in root formation. Lineage tracing showed CXCL12⁺ cells give rise to dental pulp cells, odontoblasts and cementoblasts mainly at the root area. Wnt/β-catenin signaling pathway is involved in odontoblast differentiation. In the second aim, a conditional knockout of β-catenin (Ctnnb1) in CXCL12⁺ cells showed a significant decrease in root length of all three mice molars compared to the control group, resulting from the cell fate shift into Sox9⁺ chondrocyte-like cells. Inactivated Wnt/β-catenin signaling hinders root formation, regulating CXCL12⁺ cell fate without effecting crown length or eruption height. These results carry implications to the role of Wnt/β-catenin signaling in CXCL12⁺ cells in root formation and regeneration of pulp.