title: Effects of angiotensin II type I receptor blocker losartan on orthodontic tooth movement.
abstract: BACKGROUND
  Drugs that block the renin-angiotensin system (RAS) are widely used for treating hypertension, heart and kidney failure, and the harmful effects of diabetes. Components of the RAS have been identified in various organs, but little is known of their effects on bone remodeling. The aim of this study was to evaluate whether the blockage of the RAS influences strain-induced bone remodeling in a model of orthodontic tooth movement.
  
  
  METHODS
  An orthodontic appliance was placed in C57BL6/J mice that were randomly divided into 2 groups: vehicle-treated mice (VH) and mice treated with losartan (an angiotensin II receptor blocker). Orthodontic tooth movement and the number of tartrate-resistant acid phosphatase-positive cells were determined by histopathologic analysis. The expression of mediators involved in bone remodeling was evaluated by quantitative real-time polymerase chain reaction. Blood pressure was measured before and during the experimental period.
  
  
  RESULTS
  Orthodontic tooth movement and tartrate-resistant acid phosphatase-positive cells were significantly reduced in the losartan group compared with the VH group. mRNA levels of osteoclast markers (RANK, RANKL, cathepsin K, and metalloproteinase 13) were lower in the losartan mice than in the VH group, whereas the expressions of osteoblast markers and negative regulators of bone resorption (periostin, dentin matrix protein, alkaline phosphatase, collagen 1A1, semaphorin 3A3, metalloproteinase 2, and osteoprotegerin) were higher in the VH group.
  
  
  CONCLUSIONS
  Blockage of the RAS system decreases osteoclast differentiation and activity and, consequently, results in decreased strain-induced bone remodeling in orthodontic tooth movement.
authors.affiliation: Resident, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Adriana Pedrosa
authors.initials: AP
authors.lastname: Moura
authors.affiliation: Resident, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carina Cristina
authors.initials: CC
authors.lastname: Montalvany-Antonucci
authors.affiliation: Assistant professor, Department of Cellular Biology, Institute of Biological Sciences, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Silvana Rodrigues de Albuquerque
authors.initials: SR
authors.lastname: Taddei
authors.affiliation: Postdoctoral resident, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Celso Martins
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Resident, Department of Biological Science, Faculty of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Cláudia Cristina
authors.initials: CC
authors.lastname: Biguetti
authors.affiliation: Associate professor, Department of Biological Science, Faculty of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Gustavo Pompermayer
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Associate professor, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Anderson José
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Full professor, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Associate professor, Department of Oral Pathology, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tarcília Aparecida
authors.initials: TA
authors.lastname: Silva
authors.affiliation: Associate professor, Department of Orthodontics, School of Dentistry, Pontifícal Catholic University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: ildeuandrade@pucminas.br.
authors.forename: Ildeu
authors.initials: I
authors.lastname: Andrade
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D056657:Cathepsin K / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D008437:Maxilla / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D011897:Random Allocation; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D040121:Semaphorin-3A / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D014087:Tooth Movement Techniques / Q000295:instrumentation / Q000379:methods*
chemical_list: D057911:Angiotensin Receptor Antagonists; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D053244:Osteoprotegerin; C082838:Postn protein, mouse; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D040121:Semaphorin-3A; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D019808:Losartan