title: Protective effects of the angiotensin type 1 receptor antagonist losartan in infection-induced and arthritis-associated alveolar bone loss.
abstract: OBJECTIVE
  The angiotensin type 1 (AT1) receptor has been implicated in the pathogenesis of inflammatory bone disorders. This study aimed to investigate the effect of an AT1 receptor antagonist in infection-induced and arthritis-associated alveolar bone loss in mice.
  
  
  METHODS
  Mice were subjected to Aggregatibacter actinomycetemcomitans oral infection or antigen-induced arthritis and treated daily with 10 mg/kg of the prototype AT1 antagonist, losartan. Treatment was conducted for 30 d in the infectious condition and for 17 d and 11 d in the preventive or therapeutic regimens in the arthritic model, respectively. The mice were then killed, and the maxillae, serum and knee joints were collected for histomorphometric and immunoenzymatic assays. In vitro osteoclast assays were performed using RAW 264.7 cells stimulated with A. actinomycetemcomitans lipopolysacharide (LPS).
  
  
  RESULTS
  Arthritis and A. actinomycetemcomitans infection triggered significant alveolar bone loss in mice and increased the levels of myeloperoxidase and of TRAP(+) osteoclasts in periodontal tissues. Losartan abolished such a phenotype, as well as the arthritis joint inflammation. Both arthritis and A. actinomycetemcomitans conditions were associated with the release of tumor necrosis factor alpha (TNF-α), interferon-gamma, interleukin-17 and chemokine (C-X-C motif) ligand 1 and an increased RANKL/osteoprotegerin ratio in periodontal tissues, but such expression decreased after losartan treatment, except for TNF-α. The therapeutic approach was as beneficial as the preventive one. In vitro, losartan prevented LPS-induced osteoclast differentiation and activity.
  
  
  CONCLUSIONS
  The blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects, thus protecting periodontal tissues in distinct pathophysiological conditions of alveolar bone loss.
authors.affiliation: Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.|Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: K D
authors.initials: KD
authors.lastname: Silveira
authors.affiliation: Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.|Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: C R
authors.initials: CR
authors.lastname: de Oliveira
authors.affiliation: Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Moura
authors.affiliation: Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.|Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: M F M
authors.initials: MF
authors.lastname: Madeira
authors.affiliation: Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: F M
authors.initials: FM
authors.lastname: Soriani
authors.affiliation: Department of Morphology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Department of Physics and Chemistry*, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: S Y
authors.initials: SY
authors.lastname: Fukada
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: D G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: da Silva
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001168:Arthritis / Q000150:complications* / Q000382:microbiology; D006651:Histocytochemistry; D007719:Knee Joint / Q000473:pathology; D019808:Losartan / Q000378:metabolism*; D008297:Male; D008437:Maxilla / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016871:Pasteurellaceae Infections / Q000150:complications* / Q000382:microbiology; D000067996:RAW 264.7 Cells / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044967:Serum / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan
keywords: alveolar bone; angiotensin; arthritis; losartan; periodontal disease