title: Inflammatory bone loss in experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in interleukin-1 receptor antagonist knockout mice.
abstract: The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-α) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-κB ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1α mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Izawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ishihara
authors.forename: H
authors.initials: H
authors.lastname: Mizutani
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Goto
authors.forename: E
authors.initials: E
authors.lastname: Okabe
authors.forename: H
authors.initials: H
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Y
authors.initials: Y
authors.lastname: Sugita
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: H
authors.initials: H
authors.lastname: Kamei
authors.forename: T
authors.initials: T
authors.lastname: Kikuchi
authors.forename: A
authors.initials: A
authors.lastname: Mitani
authors.forename: J
authors.initials: J
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology*; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology*; D001862:Bone Resorption / Q000209:etiology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000209:etiology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D016871:Pasteurellaceae Infections / Q000150:complications* / Q000382:microbiology; D010518:Periodontitis / Q000150:complications* / Q000382:microbiology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053244:Osteoprotegerin; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor