Constitutive activation of beta-catenin in odontoblasts induces aberrant pulp calcification in mouse incisors

摘要

During dentin formation, odontoblast polarization ensures that odontoblasts directionally secrete dentin matrix protein, leading to tubular dentin formation; however, little is known about the major features and regulatory mechanisms of odontoblast polarization. In a study of epithelial cell polarization, beta-catenin was shown to serve as a structural component of cadherin-based adherens junctions to initiate cell polarity. However, the role of beta-catenin in odontoblast polarization has not been well investigated. In this study, we explored whether beta-catenin participated in odontoblast polarization to regulate the secretion of mineralization proteins. We established Col1-CreErt2; beta-catenin exon3(fl/fl) (CA-beta-catenin) mice, which constitutively activate beta-catenin in odontoblasts. CA-beta-catenin mice exhibited disorganization and depolarization of incisor odontoblasts. Moreover, the incisor dentin was hypomineralized, and ectopic calcification was found in mouse incisor pulp. In addition, by constitutive activation of beta-catenin, the expression levels of the core polarity molecule Cdc42 and its downstream polarity protein complex Par3-Par6-aPKC were decreased in the incisors of CA-beta-catenin mice. These findings suggest that beta-catenin plays an essential role in dentin formation by regulating odontoblast polarization.