Wnt Acts as a Prosurvival Signal to Enhance Dentin Regeneration

Abstract

Wnt proteins are lipid-modified, short-range signals that control stem cell self-renewal and tissue regeneration. We identified a population of Wnt responsive cells in the pulp cavity, characterized their function, and then created a pulp injury. The repair response was evaluated over time using molecular, cellular, and quantitative assays. We tested how healing was impacted by wound environments in which Wnt signaling was amplified. We found that a Wnt-amplified environment was associated with superior pulp healing. Although cell death was still rampant, the number of cells undergoing apoptosis was significantly reduced. This resulted in significantly better survival of injured pulp cells, and resulted in the formation of more tertiary dentin. We engineered a liposomereconstituted form of WNT3A then tested whether this biomimetic compound could activate cells in the injured tooth pulp and stimulate dentin regeneration. Pulp cells responded to the elevated Wnt stimulus by differentiating into secretory odontoblasts. Thus, transiently amplifying the body's natural Wnt response resulted in improved pulp vitality. These data have direct clinical implications for treating dental caries, the most prevalent disease affecting mankind.

The Role of Autonomous Wntless in Odontoblastic Differentiation of Mouse Dental Pulp Cells

“…In general, injury activates the endogenous Wnt pathway 24,25) . In a recent pulp cavity animal model, the response to pulpal injury was similar as shown that elevating Wnt signaling by either removing a negative Wnt regulator or by providing exogenous WNT3A protein was sufficient to significantly improve the pulp cavity's repair response 22) . In this model, pulp cells responded to the elevated Wnt stimulus by differentiating into secretory odontoblasts.…”

“…The formation of reparative dentin needs the recruitment and proliferation of pulp cells, which might be re-activated after injury. At the injured site, pulp cells needs to proliferate and differentiate into odontoblast-like cells 22) . The adult pulp contains a heterogeneous cell population including odontoblast progenitor cells and consisting of fibroblast-like cells, macrophages and other nerve or capillary cells 20,23) .…”

Exploiting the WNT Signaling Pathway for Clinical Purposes

“…The findings include regulation of pulp volume and dentin thickness [110], enhancement of dentin regeneration [111], and cementum regeneration [112]. Tooth movement during orthodontic treatment has also been shown to involve activation of Wnt signaling [113,114].…”

Dental mesenchymal stem cells

“…The signals that mobilize the dental MSCs and stimulate their differentiation are poorly understood, but are known to involve the release of sequestered TGF-β following physical damage and Wnt signals that regulate pulp cell apoptosis, among other functions (Hunter et al, 2015). The presence of latent TGF-β proteins in dentine tubules and its activity in promoting reparative dentine formation has recently been exploited in a potential clinical device involving the delivery of low energy laser light to stimulate liberation of TGF-β (Arany et al, 2014).…”