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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00307

Resolvin D2 Induces Resolution of Periapical Inflammation and Promotes Root Apex Calcification in Rat Periapical Periodontitis.

  • 1Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Japan
  • 2Department of Periodontics and Endodontics, Okayama University Hospital, Japan
  • 3Center for Innovative Clinical Medicine, Okayama University Hospital, Japan
  • 4Ministry of Health Labour and Welfare, Japan
  • 5Department of Molecular Biology and Biochemistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Japan
  • 6Center for Clinical and Translational Research, Forsyth Institute, United States

Periapical periodontitis results from pulpal infection leading to pulpal necrosis and resorption of periapical bone. The current treatment is root canal therapy, which attempts to eliminate infection and necrotic tissue. But, in some cases periapical inflammation doesn’t resolve even after treatment. Resolvins are part of a large family of specialized pro-resolving lipid mediators that actively resolves inflammation signalling via specific receptors. Resolvin D2 (RvD2), a metabolite of docosahexaenoic acid (DHA), was tested as an intracanal medicament in rats in vivo. Mechanism was evaluated in rat primary dental pulp cells (DPCs) in vitro. The results demonstrate that RvD2 reduces inflammatory cell infiltrate, bacterial load and periapical lesion size, and fosters pulp like tissue regeneration and root apex calcification. RvD2 enhanced expression of its receptor, GPR18, and dentin matrix acidic phosphoprotein 1 (DMP1) in vivo and in vitro. Moreover, RvD2 induces phosphorylation of Stat3 transcription factor in dental pulp cells. We conclude that intracanal treatment with RvD2 resolves inflammation and increases efficiency of bacterial clearance promoting root apex calcification and healing of periapical bone lesions. The data suggest that RvD2 induced active resolution of inflammation is suitable for healing of periapical lesions, with pulp-like tissue regeneration after root canal infection.

Keywords: Resolvin D2, resolution of periapical inflammation, DMP1, Periapical Periodontitis, calcification

Received: 06 Nov 2018; Accepted: 06 Feb 2019.

Edited by:

Philippe Saas, INSERM U1098 Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, France

Reviewed by:

Janos G. Filep, Université de Montréal, Canada
Maria Balta, University of Oslo, Norway
Chun-Teh Lee, School of Dentistry, University of Texas Health Science Center at Houston, United States  

Copyright: © 2019 Siddiqui, Omori, Ito, Yamashiro, Nakamura, Okamoto, Ono, Yamamoto, Van Dyke and Takashiba. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Shogo Takashiba, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan, stakashi@okayama-u.ac.jp