Activation of Wnt signaling in Axin2+ cells leads to osteodentin formation and cementum overgrowth

Abstract

Objectives: In this study, we used the mouse incisor model to investigate the regulatory mechanisms of Wnt/β-catenin signaling on Axin2⁺ cells in tooth development.

Materials and methods: Axin2^lacZ/+ reporter mice were used to define the expression pattern of Axin2 in mouse incisors. We traced the fate of Axin2⁺ cells from postnatal Day 21 (P21) to P56 using Axin2^CreERT2/+ and R26R^tdTomato/+ reporter mice. For constitutive activation of Wnt signaling, Axin2^CreERT2/+ , β-catenin^flox(Ex3)/+ , and R26R^tdTomato/+ (CA-β-cat) mice were generated to investigate the gain of function (GOF) of β-catenin in mouse incisor growth.

Results: The X-gal staining of Axin2^lacZ/+ reporter mice and lineage tracing showed that Axin2 was widely expressed in dental mesenchyme of mouse incisors, and Axin2⁺ cells were essential cell sources for odontoblasts, pulp cells, and periodontal ligament cells. The constitutive activation of Wnt signaling in Axin2⁺ cells resulted in the formation of osteodentin featured with increased DMP1 and dispersed DSP expression and overgrowth of cementum.

Conclusion: Wnt signaling plays a key role in the differentiation and maturation of Axin2⁺ cells in mouse incisors.

Keywords: Axin2; Wnt/β-catenin signaling; cementum; dentin; mouse incisor.