title: Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth.
abstract: Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation.
authors.affiliation: Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Fanny
authors.initials: F
authors.lastname: Chmilewsky
authors.affiliation: Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Warda
authors.initials: W
authors.lastname: Ayaz
authors.affiliation: Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: James
authors.initials: J
authors.lastname: Appiah
authors.affiliation: Aix-Marseille Université, CNRS, ISM UMR 7287, 13288, Marseille cedex 09, France.
authors.forename: Imad
authors.initials: I
authors.lastname: About
authors.affiliation: Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Seung-Hyuk
authors.initials: SH
authors.lastname: Chung
mesh_terms: D018920:Coculture Techniques; D003782:Dental Pulp / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000473:pathology; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D017213:Root Caries / Q000378:metabolism* / Q000473:pathology
chemical_list: C488033:C5AR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D020932:Nerve Growth Factor