title: Reactionary Dentinogenesis and Neuroimmune Response in Dental Caries.
abstract: Reactionary dentin formation is an adaptive secretory response mediated by odontoblasts to moderate dentin injury. The implications of this process for neuroimmune interactions operating to contain pathogens have not been fully appreciated. The purpose of the present study was to describe the relationship between reactionary dentinogenesis, the neurogenic changes of dental pulp innervation, and dendritic cell recruitment to caries progression, using a comparative immunohistochemical approach in human teeth from young adult individuals. Reactionary dentin formation during dentin caries progression is associated with changes in the integrity of junctional complexes within the odontoblast layer. Diminished coexpression of Cx43 and zonula occludens 1 implies a reduced level of intercellular connectivity between odontoblasts. Dentin caries also causes overexpression of growth-associated protein 43, a modulator of neural plasticity that promotes extensive sprouting of nerve endings into the reactionary dentin matrix. At the same time, an elevated number of HLA-DR-positive dendritic cells infiltrate the odontoblast layer and subsequently invade reactionary dentin formed underneath the early caries-affected regions. Simultaneous odontoblast layer remodeling, nerve fiber sprouting, and activation of dendritic cells during caries progression suggest a coordinated neuroimmune response to fight caries pathogen invasion and to promote dentin-pulp healing. We propose that reactionary dentin formation hinders pathogen invasion and supports defensive neuroimmune interactions against infection. The eventual understanding of this complex scenario may contribute to the development of novel approaches to dental caries treatment.
authors.affiliation: Instituto de Biología, Laboratorio de Microscopía Electrónica Centro Interdisciplinario de Neurociencia de Valparaíso Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile eduardo.couve@uv.cl.
authors.forename: E
authors.initials: E
authors.lastname: Couve
authors.affiliation: Instituto de Biología, Laboratorio de Microscopía Electrónica Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Osorio
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: O
authors.initials: O
authors.lastname: Schmachtenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement / Q000502:physiology; D018031:Connexin 43 / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D003731:Dental Caries / Q000473:pathology*; D003782:Dental Pulp / Q000276:immunology / Q000294:innervation; D003809:Dentin, Secondary / Q000276:immunology / Q000294:innervation / Q000473:pathology*; D003810:Dentinogenesis / Q000276:immunology / Q000502:physiology*; D018450:Disease Progression; D019922:GAP-43 Protein / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007365:Intercellular Junctions / Q000473:pathology; D009411:Nerve Endings / Q000648:ultrastructure; D009412:Nerve Fibers / Q000648:ultrastructure; D015213:Neuroimmunomodulation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009804:Odontoblasts / Q000473:pathology; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000032:analysis
chemical_list: D018031:Connexin 43; D019922:GAP-43 Protein; D006684:HLA-DR Antigens; D062826:Zonula Occludens-1 Protein
keywords: Cx43; ZO-1; dendritic cell; nociceptor; odontoblast; pain