title: Interleukin-33 and RANK-L Interplay in the Alveolar Bone Loss Associated to Periodontitis.
abstract: BACKGROUND
  Chronic Periodontitis (CP) is an inflammatory disease of bacterial origin that results in alveolar bone destruction. Porphyromonas gingivalis (Pg), one of the main periopathogens, initiates an inflammatory cascade by host immune cells thereby increasing recruitment and activity of osteoclasts, the bone resorbing cells, through enhanced production of the crucial osteoclastogenic factor, RANK-L. Antibodies directed against some cytokines (IL-1β, IL-6 and TNF-α) failed to exhibit convincing therapeutic effect in CP. It has been suggested that IL-33, could be of interest in CP.
  
  
  OBJECTIVE
  the present study aims to analyze whether and how IL-33 and RANK-L and/or their interplay are involved in the bone destruction associated to CP.
  
  
  METHODS
  mRNAs and protein expressions of IL-33 and RANK-L were analyzed in healthy and CP human gingival samples by immunohistochemistry (IHC) and RT-qPCR. Murine experimental periodontitis (EP) was induced using Pg infected ligature and Pg free ligature around the first maxillary molar. Alveolar bone loss was recorded by μCT. Mouse gingival explants were stimulated for 24 hours with IL-33 and RANK-L mRNA expression investigated by RT-qPCR. Human oral epithelial cells were infected by Pg for 6, 12; 24 hours and IL-33 and RANK-L mRNA expressions were analyzed by RT-qPCR.
  
  
  RESULTS
  IL-33 is overexpressed in gingival epithelial cells in human affected by CP as in the murine EP. In human as in murine gingival cells, RANK-L was independently induced by Pg and IL-33. We also showed that the Pg-dependent RANK-L expression in gingival epithelial cells occured earlier than that of IL-33.
  
  
  CONCLUSIONS
  Our results evidence that IL-33 overexpression in gingival epithelial cells is associated with CP and may trigger RANK-L expression in addition to a direct effect of Pg. Finally, IL-33 may act as an extracellular alarmin (danger signal) showing proinflammatory properties in CP perpetuating bone resorption induced by Pg infection.
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lapérine
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.|ONIRIS, UMR-S 791, LIOAD, Nantes, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cloitre
authors.affiliation: EA 3826 Thérapeutiques cliniques et expérimentales des infections, Nantes, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.affiliation: INSERM, U1109 Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Département de Parodontologie, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huck
authors.affiliation: INSERM, U1109 Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Isaac Maximiliano
authors.initials: IM
authors.lastname: Bugueno
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.|ONIRIS, UMR-S 791, LIOAD, Nantes, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sourice
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Le Tilly
authors.affiliation: Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva, Switzerland.|Department of Pathology-Immunology, University of Geneva, School of Medicine, Geneva, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.affiliation: INSERM, U1109 Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Département de Parodontologie, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davideau
authors.affiliation: INSERM U1132 BIOSCAR, Hôpital Lariboisière, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Geoffroy
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.|ONIRIS, UMR-S 791, LIOAD, Nantes, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beck-Cormier
authors.affiliation: INSERM, U791, LIOAD, Nantes, France.|Université de Nantes, UMR-S 791, LIOAD, Nantes, France.|UFR Odontologie, Nantes, France.|ONIRIS, UMR-S 791, LIOAD, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesclous
mesh_terms: D000293:Adolescent; D000328:Adult; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D016966:Porphyromonas gingivalis / Q000472:pathogenicity; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D055114:X-Ray Microtomography; D055815:Young Adult
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D053245:RANK Ligand; C505688:TNFSF11 protein, human