Deficiency of Sensory Afferents Impairs Dental Pulp Stem Cells (DPSCs) in a Mouse Model of Pulpitis

Abstract

Vital pulp therapy has recently gained traction within the endodontic community as a more conservative and biologically driven alternative to traditional root canal treatment. While sensory nerves are primarily known for their role in pain perception, emerging evidence suggests they also contribute significantly to tissue repair by regulating dental pulp stem cells. However, the precise mechanisms underlying the interaction between sensory nerves and dental pulp stem cells during injury repair remain poorly understood. This study investigates whether sensory nerve deafferentation affects DPSC-mediated homeostasis and the injury repair process in pulpitis. Using a Gli1-CreER/Rosa26-tdTomato mouse model, we performed inferior alveolar nerve deafferentation followed by a dental pulp capping procedure. Single-cell RNA sequencing post-deafferentation revealed a phenotypic shift in Schwann cell clusters, transitioning from a non-myelinated to a myelinated state. Additionally, a significant increase in immune cell populations was observed, indicative of heightened pulpal inflammation following sensory nerve loss. Importantly, sensory nerve deafferentation led to a marked reduction in Gli1⁺ cell aggregation and impaired tertiary dentin formation at the site of pulp capping. These findings suggest that sensory nerves play a pivotal regulatory role in guiding the migration and differentiation of Gli1⁺ cells into odontoblast-like cells, which are essential for effective tertiary dentinogenesis. This study illuminates a previously underexplored dimension of vital pulp therapy, emphasizing the potential role of sensory afferents and their associated molecular mediators in orchestrating mesenchymal stem cell behavior—particularly their migration and transdifferentiation—during the reparative response to pulpal injury.