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

Abstract

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 Axin2CreERT2/+; R26RtdTomato/+ mice with β‐cateninflox/flox 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.

Acellular Extrinsic Fiber Cementum Is Invariably Present in the Superficial Layer of Apical Cementum in Mouse Molar

“…30 The constitutive activation of β-catenin in Wnt-responsive Gli1-or Axin2-lineage cells results in cementum hyperplasia, 3,19 whereas the loss of β-catenin in these cells leads to cementum hypoplasia. 19,31 Consistent with the findings of a previous study, 32 the present study revealed that the production of sclerostin in cementocytes increased with age, whereas the production of β-catenin in PDL cells remained unchanged. Occlusal unloading increases the production of sclerostin in osteocytes, resulting in periodontal tissue destruction due to the limited propagation of Gli1-lineage tissue stem cells.…”