Loss of β-catenin causes cementum hypoplasia by hampering cementogenic differentiation of Axin2-expressing cells.

Background And Objective: Although cementum plays an essential role in tooth attachment and adaptation to occlusal force, the regulatory mechanisms of cementogenesis remain largely unknown. We have previously reported that Axin2-expressing (Axin2 ) mesenchymal cells in periodontal ligament (PDL) are the main cell source for cementum growth, and constitutive activation of Wnt/β-catenin signaling in Axin2 cells results in hypercementosis. Therefore, the aim of the present study was to further evaluate the effects of β-catenin deletion in Axin2 cells on cementogenesis.

Materials And Methods: We generated triple transgenic mice to conditionally delete β-catenin in Axin2-lineage cells by crossing Axin2 ; R26R mice with β-catenin mice. Multiple approaches, including X-ray analysis, micro-CT, histological stainings, and immunostaining assays, were used to analyze cementum phenotypes and molecular mechanisms.

Results: Our data revealed that loss of β-catenin in Axin2 cells led to a cementum hypoplasia phenotype characterized by a sharp reduction in the formation of both acellular and cellular cementum. Mechanistically, we found that conditional removal of β-catenin in Axin2 cells severely impaired the secretion of cementum matrix proteins, for example, bone sialoprotein (BSP), dentin matrix protein 1 (DMP1) and osteopontin (OPN), and markedly inhibited the differentiation of Axin2 mesenchymal cells into osterix cementoblasts.

Conclusions: Our findings confirm the vital role of Axin2 mesenchymal PDL cells in cementum growth and demonstrate that Wnt/β-catenin signaling shows a positive correlation with cementogenic differentiation of Axin2 cells.