Modulators of Wnt Signaling Pathway Implied in Dentin Pulp Complex Engineering: A Literature Review

Abstract

The main goal of vital pulp therapy (VPT) is to preserve the vitality of the pulp tissue, even when it is exposed due to bacterial invasion, iatrogenic mechanical preparation, or trauma. The type of new dentin formed as a result of VPT can differ in its cellular origin, its microstructure, and its barrier function. It is generally agreed that the new dentin produced by odontoblasts (reactionary dentin) has a tubular structure, while the dentin produced by pulp cells (reparative dentin) does not or has less. Thus, even VPT aims to maintain the vitality of the pulp. It does not regenerate the dentin pulp complex integrity. Therefore, many studies have sought to identify new therapeutic strategies to successfully regenerate the dentin pulp complex. Among them is a Wnt protein-based strategy based on the fact that Wnt proteins seem to be powerful stem cell factors that allow control of the self-renewal and proliferation of multiple adult stem cell populations, suitable for homeostasis maintenance, tissue healing, and regeneration promotion. Thus, this review outlines the different agents targeting the Wnt signaling that could be applied in a tooth environment, and could be a potential therapy for dentin pulp complex and bone regeneration.

Keywords: Wnt signal; dentin pulp complex regeneration engineering; small molecules.

Figure 1

Schematic illustration of the canonical Wnt pathway. (A). In the presence of Wnt ligands interacting with LRP5/6 and frizzled, the β-catenin degradation complex is sequestrated. Cytosolic accumulation of β-catenin leads to nuclear translocation and binding to transcription factors in the Lef/Tcf family. The resulting active transcriptional complex controls the expression of target genes involved in tissue generation, regeneration and, self-renewal. (B). In the absence of Wnt ligands, the interaction between DVL and axin leads to the phosphorylation of cytosolic β-catenin by a protein complex involving APC, axin, and GSK3. β-catenin is then degraded by ubiquitin-mediated proteolysis. LRP: lipoprotein receptor-related protein. DVL: dishevelled-APC: adenomatosis polyposis coli. GSK: glycogen synthase kinase. TCF/Lef1: T-cell factor/lymphoid enhancer factor. DPSCs: dental pulp stem cells. SCAPs: stem cells from apical papilla.

Figure 2

Schematic illustration of the clinical application of Wnt/β-catenin enhancers.