Investigation of Dentin Regeneration via Neurotransmitters and Innate Immune Regulation during Pulp Healing

抄録

 Purpose: The purpose of this study was to elucidate the roles of the neurotransmitter calcitonin gene-related peptide (CGRP) and innate immune regulation to investigate dentin regeneration during the pulp healing process.

 Methods: Experimental dental pulp injury was induced in 8-week-old Wistar rats by making group cavities in the mesial proximal surface of the maxillary first molars. Histologic analyses were performed postoperatively at 1, 3, 5, 7, and 14 days. The pathological condition of the dental pulp and periapical periodontal tissues was examined by hematoxylin and eosin staining; the dynamics of odontoblasts were evaluated with anti-nestin antibodies; apoptosis was assessed by TdT-mediated dUTP nick-end labeling (TUNEL) assay; cell proliferation was measured with anti-Ki67 antibodies; and the dynamics of nerve fibers, M2 macrophages and dendritic cells, and CGRP expression patterns were analyzed with anti-PGP9.5, anti-CD206, and anti-CGRP antibodies, respectively.

 Results: Infiltration of inflammatory cells, mainly of polymorphonuclear leukocytes and macrophages, was strong on postoperative day 1 and decreased over time. In contrast, the positivity rates for nestin, PGP9.5, and Ki-67 peaked between postoperative days 3 and 5 and then decreased. CGRP positivity rates increased at the dentin-pulp interface directly beneath the cavity from postoperative day 7 to day 14, and the area of reparative dentin also increased from postoperative day 5.

 Conclusion: In dental pulp tissue, the anti-infection function of innate immune-related cells, enhanced by neuropeptide CGRP production, promotes the formation of reparative dentin during the pulp healing process after dental injury.