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 beta-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(CreERT2/+); R26R(DTA/+) mice led to severe cementum hypoplasia, whereas constitutive activation of beta-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.