Regulation of Reactionary Dentine Formation

During the treatment of dental caries that has not penetrated the tooth pulp, maintenance of as much unaffected dentine as possible is a major goal during the physical removal of decayed mineral. Damage to dentine leads to release of fossilized factors (transforming growth factor-beta [TGF-beta] and bone morphogenic protein [BMP]) in the dentine that are believed to stimulate odontoblasts to secrete new tertiary dentine (reactionary dentine). This is formed on the pulpal surface of existing dentine and rethickens the dentine. We have previously shown that activation of Wnt/-catenin signaling is pivotal for tooth repair in exposed pulp injury, and the pathway can be activated by small-molecule GSK-3 antagonists, resulting in enhanced reparative dentine formation. Here, we use a nonexposed pulp injury model to investigate the mechanisms of reactionary dentine formation in vivo, using small molecules to modulate the Wnt/beta-catenin, TGF-beta, and BMP pathways. We found that a local increase of Wnt activation at the injury site enhances reactionary dentine secretion. In addition, inhibition of TGF-beta, BMP, or Wnt pathways does not impede reactionary dentine formation, although inhibition of TGF-beta and/or BMP signaling does result in more disorganized, nontubular reactionary dentine. This suggests that Wnt/beta-catenin signaling plays no major role in the formation of reactionary dentine, but in common with reparative dentine formation, exogenous elevation of Wnt/beta-catenin signaling can enhance tertiary dentine formation. Release of latent TGF-beta or BMPs from dentine is not required for the deposition of mineral to form reactionary dentine but does play a role in its organization.