Axin2⁺-Mesenchymal PDL Cells, Instead of K14⁺ Epithelial Cells, Play a Key Role in Rapid Cementum Growth

To date, attempts to regenerate functional periodontal tissues (including cementum) are largely unsuccessful due to a lack of full understanding about the cellular origin (epithelial or mesenchymal cells) essential for root cementum growth. To address this issue, we first identified a rapid cementum growth window from the ages of postnatal day 28 (P28) to P56. Next, we showed that expression patterns of Axin2 and β-catenin within cementum-forming periodontal ligament (PDL) cells are negatively associated with rapid cementum growth. Furthermore, cell lineage tracing studies revealed that the Axin2⁺-mesenchymal PDL cells and their progeny rapidly expand and directly contribute to postnatal acellular and cellular cementum growth. In contrast, the number of K14⁺ epithelial cells, which were initially active at early stages of development, was reduced during rapid cementum formation from P28 to P56. The in vivo cell ablation of these Axin2⁺ cells using Axin2; R26R mice led to severe cementum hypoplasia, whereas constitutive activation of β-catenin in the Axin2⁺ cells resulted in an acceleration in cellular cementogenesis plus a transition from acellular cementum to cellular cementum. Thus, we conclude that Axin2⁺-mesenchymal PDL cells, instead of K14⁺ epithelial cells, significantly contribute to rapid cementum growth.