Pulp Fibroblasts Control Nerve Regeneration through Complement Activation

• Published in: Journal of dental research Vol. 95; no. 8; pp. 913 - 922
• Main Authors: Chmilewsky, F., About, I., Chung, S.-H.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2016; SAGE PUBLICATIONS, INC; SAGE Publications (UK and US)
• Subjects: Anaphylatoxins; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - physiology; Cells, Cultured; Complement activation; Complement Activation - physiology; Complement component C5a; Dental caries; Dental pulp; Dental Pulp - cytology; Dental Pulp - innervation; Dental Pulp - physiology; Dentin; Dentin - physiology; Dentistry; Fibroblasts; Fibroblasts - physiology; Fluorescent Antibody Technique; Growth factors; Humans; Immune response; Inflammation; Life Sciences; Lipoteichoic acid; Nerve Fibers - physiology; Nerve Regeneration - physiology; Receptor, Anaphylatoxin C5a - metabolism; Regeneration; Teeth; Tissue engineering; pulp biology; receptor biology; cell biology; innate immunity; axon outgrowth; caries
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034516643065

Dentin-pulp regeneration is closely linked to the presence of nerve fibers in the pulp and to the healing mechanism by sprouting of the nerve fiber’s terminal branches beneath the carious injury site. However, little is known about the initial mechanisms regulating this process in carious teeth. It has been recently demonstrated that the complement system activation, which is one of the first immune responses, contributes to tissue regeneration through the local production of anaphylatoxins such as C5a. While few pulp fibroblasts in intact teeth and in untreated fibroblast cultures express the C5a receptor (C5aR), here we show that all dental pulp fibroblasts, localized beneath the carious injury site, do express this receptor. This observation is consistent with our in vitro results, which showed expression of C5aR in lipoteichoic acid–stimulated pulp fibroblasts. The interaction of C5a, produced after complement synthesis and activation from pulp fibroblasts, with the C5aR of these cells mediated the local brain-derived neurotropic factor (BDNF) secretion. Overall, this activation guided the neuronal growth toward the lipoteichoic acid–stimulated fibroblasts. Thus, our findings highlight a new mechanism in one of the initial steps of the dentin-pulp regeneration process, linking pulp fibroblasts to the nerve sprouting through the complement system activation. This may provide a useful future therapeutic tool in targeting the fibroblasts in the dentin-pulp regeneration process.