Study of osteo-nociceptive-immune system

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H05686
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: Maruyama Kenta 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (60724119)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 骨代謝 / 真菌感染 / 痛覚

Outline of Final Research Achievements

It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce CGRP. This induction of CGRP is independent of Bcl-10 or Malt-1 but dependent on TRPV1/TRPA1 ion channels. Hind paw β-glucan injection after Nav1.8-positive nociceptor ablation or in TRPV1/TRPA1 deficiency showed dramatically increased osteo-inflammation accompanied by impaired CGRP production. Strikingly, CGRP suppressed β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of NF-κB p65 by the transcriptional repressor Jdp2 and inhibition of actin polymerization, respectively. These findings clearly suggest the role of Dectin-1-mediated sensocrine pathways in the resolution of fungal osteo-inflammation.

Free Research Field

骨代謝学