title: Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: comparison with RANKL-overexpressing transgenic male mice.
abstract: Periodontitis, an inflammatory disease of periodontal tissues, is characterized by excessive alveolar bone resorption. An increase in the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio is thought to reflect the severity of periodontitis. Here, we examined alveolar bone loss in OPG-deficient (OPG(-/-)) mice and RANKL-overexpressing transgenic (RANKL-Tg) mice. Alveolar bone loss in OPG(-/-) mice at 12 weeks was significantly higher than that in RANKL-Tg mice. OPG(-/-) but not RANKL-Tg mice exhibited severe bone resorption especially in cortical areas of the alveolar bone. An increased number of osteoclasts was observed in the cortical areas in OPG(-/-) but not in RANKL-Tg mice. Immunohistochemical analyses showed many OPG-positive signals in osteocytes but not osteoblasts. OPG-positive osteocytes in the cortical area of alveolar bones and long bones were abundant in both wild-type and RANKL-Tg mice. This suggests the resorption in cortical bone areas to be prevented by OPG produced locally. To test the usefulness of OPG(-/-) mice as an animal model for screening drugs to prevent alveolar bone loss, we administered an antimouse RANKL antibody or risedronate, a bisphosphonate, to OPG(-/-) mice. They suppressed alveolar bone resorption effectively. OPG(-/-) mice are useful for screening therapeutic agents against alveolar bone loss.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, Nagano 399-0781, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Koide
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Midori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Arai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Okahashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yoshinari
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D008297:Male; D008336:Mandibular Diseases / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism; D053244:Osteoprotegerin; D010518:Periodontitis; D053245:RANK Ligand
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand