Neuro-immunological mechanism of retrogradely-transported peptides in oral diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu Dental College
• Principal Investigator: Kentaro Ono 九州歯科大学, 歯学部, 教授 (40316154)
• Co-Investigator(Kenkyū-buntansha): 人見 涼露 日本大学, 歯学部, 講師 (70548924)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ヘプシジン / 三叉神経節ニューロン / 口内炎 / 歯周炎 / 下歯槽神経障害 / 抗菌ペプチド / 疼痛

Outline of Final Research Achievements

The purpose of this study was to elucidate the effects of antimicrobial peptides induced in a nerve-specific manner in oral diseases such as oral ulcer, periodontitis, and inferior alveolar nerve injury. In a validation of the effect of steroid drug in a rat model of oral ulcer, the drug suppressed pain although the rate of healing was not changed. In a comprehensive genetic analysis from the trigeminal ganglion of the model, the gene for hepcidin, an antimicrobial peptide, was most elevated. The gene was specifically elevated at the site of disease and in the innervating ganglion, as was the case in the periodontitis and nerve injury models. Electrophysiological analysis showed that hepcidin enhanced the neural response to nociceptive mechanical stimulation in the oral mucosa. The present study demonstrate the involvement of hepcidin in oral neuroimmunological mechanisms.

Free Research Field

口腔病態生理学

Academic Significance and Societal Importance of the Research Achievements

口腔内には常在細菌がいるため、疾患発生には感染が付きものである。本研究にて抗菌ペプチドのヘプシジンが発現上昇する反応は種々の口腔内疾患モデルで共通して観察されており、口腔内疾患の成立機序を考えると理にかなった生体防御機構であると考えられる。また、ヘプシジンは疼痛を増強する作用を持っており、疼痛発生にて疾患部位を個体に認知・警告している可能シ性がある。本研究にて明らかにしたヘプシジン作用機構は種々の口腔疾患で共通しているため、口腔疾患の包括的治療を計画する際に非常に有用な情報を提供し、ヘプシジンは治療標的の1つとなり得る。