Vital pulp
therapy and
root canal therapy (RCT) are the dominant treatment for irreversible
pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of
inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of
Resolvin E1 (
RvE1)
therapy in dental pulp regeneration and the impact of
RvE1 in infected pulps. We investigated the actions of
RvE1 on experimentally exposed pulps with or without microbial
infection in an Axin2Cre-Dox;Ai14 genetically defined mouse model. Our results showed
RvE1 promoted Axin2-tdTomato+ cell expansion and odontoblastic differentiation after direct
pulp capping in the mouse, which we used to mimic reversible
pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs),
RvE1 facilitated Axin2-tdTomato+ cell proliferation and odontoblastic differentiation and also rescued impaired functions after
lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h,
RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of
apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with
RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of
inflammation, reduced
infection severity, and prevented
apical periodontitis, presenting
RvE1 as a novel therapeutic for treating endodontic diseases.