title: Ligature induced peri-implantitis: tissue destruction and inflammatory progression in a murine model.
abstract: OBJECTIVE
  The aim of this study was to investigate tissue destruction and inflammatory progression of ligature-induced peri-implantitis in mice and to establish an alternative murine model of peri-implantitis.
  
  
  METHODS
  Sixty male C57BL/6NCrSlc mice (4-week-old) were used and the maxillary right first molars were extracted. Eight weeks after extraction, custom-made pure titanium machined screw type implants (0.8 × 1.5 mm) were placed, one implant per animal. Four weeks later, 5-0 silk ligatures were applied around implant necks to induce peri-implantitis. Animals were sacrificed at 0 (before ligature), 7, 14, 21 and 28 days after ligature. Half of the samples were analyzed radiologically and histologically to measure bone level change, osteoclast number, density, and distribution. The rest of the samples was used to determine the relative mRNA expression levels of IL-1 and TNF-α with RT-PCR analysis.
  
  
  RESULTS
  Bone levels at all sites (buccal, palatal, mesial, distal) decreased 40-50% significantly 28 days after ligature (P < 0.01). Osteoclast number at all post-ligature time points increased significantly (P < 0.05). However, their density at day 28 decreased significantly compared to that of day 21 (P < 0.05). Accordingly, IL-1 and TNF-α mRNA expression increased significantly at the early time points but decreased significantly at day 28 after ligature (P < 0.05).
  
  
  CONCLUSIONS
  Inflammatory response followed by significant peri-implant bone resorption suggested 28 days ligation is sufficient to successfully induce peri-implantitis in the current mice model. This model might open a new avenue to study the pathogenesis and mechanism of peri-implantitis.
authors.affiliation: Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Trang N
authors.initials: TN
authors.lastname: Nguyen Vo
authors.affiliation: Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Jia
authors.initials: J
authors.lastname: Hao
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
authors.forename: Josh
authors.initials: J
authors.lastname: Chou
authors.affiliation: Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Boosana
authors.initials: B
authors.lastname: Kaboosaya
authors.affiliation: Department of Oral Implantology and Regenerative Dental Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kasugai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D008026:Ligation; D008297:Male; D008437:Maxilla / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D057873:Peri-Implantitis / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha
keywords: bone resorption; ligature; murine model; osteoclasts; peri-implantitis; preinflammatory cytokine