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

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.Axin2lacZ/+ 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 Axin2CreERT2/+ and R26RtdTomato/+ reporter mice. For constitutive activation of Wnt signaling, Axin2CreERT2/+ , β-cateninflox(Ex3)/+ , and R26RtdTomato/+ (CA-β-cat) mice were generated to investigate the gain of function (GOF) of β-catenin in mouse incisor growth.The X-gal staining of Axin2lacZ/+ 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.Wnt signaling plays a key role in the differentiation and maturation of Axin2+ cells in mouse incisors.