Vdr mediates Wnt signaling pathway to regulate odontoblasts differentiation during dentin apposition

Abstract

Dentin, a complex, living, and porous mineral substance, is produced by the mineralization of predentin, which is secreted by odontoblasts. This substance is crucial for maintaining the health of teeth. However, the specific function of the vitamin D receptor (Vdr) in the mineralization of odontoblasts, dentin homeostasis, and its interaction with Wnt signaling pathway during dentin apposition is not well understood. In this study, we employed Vdr transgenic knockout mice to study the dental effects and observed enlarged pulp cavities, diminished dentin, and increased predentin thickness in Vdr^−/− mice. We further reduced Vdr expression in odontoblasts and analyzed the changes in mineralization and Wnt signaling pathway. Our results showed decreased levels of mineralization and its markers Dspp, Alpl, Opn, Col-1, and Bsp in Vdr-knockdown odontoblasts. Additionally, the Wnt signaling pathway was downregulated, as indicated by lower levels of β-catenin, Lef1, and Axin2, and higher levels of Dkk1. We then attempted to rescue these effects by treating them with lithium chloride (LiCl) which activated the Wnt signaling pathway and appeared to restore the mineralization capacity of odontoblasts. Overall, our findings suggest that Vdr can mediate the Wnt signaling pathway to regulate odontoblasts differentiation during dentin apposition, presenting new potential approaches for improving dental health.