title: A novel gingival overgrowth mouse model induced by the combination of CsA and ligature-induced inflammation.
abstract: Drug-induced gingival overgrowth (DIGO) is a side effect of the enlargement of gingival tissue by phenytoin, nifedipine, and cyclosporine A (CsA). Gingival inflammation has been identified as a key factor that initiates DIGO. However, a sufficient animal model for clarifying the role of inflammation in DIGO has not yet been generated. We herein describe a novel CsA-induced gingival overgrowth mouse model to evaluate the role of inflammation. A ligature was placed around the second molar in maxillae for 7days to induce gingival inflammation, and CsA (50mg/kg/day) was administered to mice during each experimental period. The severity of gingival overgrowth and mRNA expression of inflammatory cytokines in gingiva were assessed by the gingival overgrowth degree, histological analyses, and RT-PCR. The administration of CsA for 28days in combination with ligation significantly increased the gingival overgrowth degree and expanded the connective tissue area. Increases in the gingival overgrowth degree continued in a time-dependent manner until 21days. Furthermore, the cessation of CsA reduced gingival overgrowth. Thin ligatures (7-0 size) induced weaker tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 mRNA expression and less gingival overgrowth than thick ligatures (5-0 ligature). Moreover, the administration of an antibiotic cocktail, which suppressed the expression of these inflammatory cytokines in gingiva, attenuated gingival overgrowth induced by ligatures and CsA. These results suggest that inflammation in gingival tissue plays a role in initiating CsA-induced gingival overgrowth. This gingival overgrowth mouse model has potential for elucidating the etiology of DIGO from the view point of gingival inflammation.
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Okanobu
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan. Electronic address: matsudas@hiroshima-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kittaka
authors.affiliation: Department of Biological Endodontics, Integrated Health Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D019214:Gingival Overgrowth / Q000276:immunology / Q000628:therapy*; D007249:Inflammation / Q000276:immunology*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016572:Cyclosporine
keywords: Cyclosporine A; Drug-induced gingival overgrowth; Ligature-induced gingival inflammation