title: Role of CCR2 in orthodontic tooth movement.
abstract: BACKGROUND
  Cytokines and chemokines regulate bone remodeling during orthodontic tooth movement. CC chemokine ligand 2 (CCL2) is involved in osteoclast recruitment and activity, and its expression is increased in periodontal tissues under mechanical loading. In this study, we investigated whether the CC chemokine receptor 2 (CCR2)-CCL2 axis influences orthodontic tooth movement.
  
  
  METHODS
  A coil spring was placed in CCR2-deficient (CCR2(-/-)), wild-type, vehicle-treated, and P8A-treated (CCL2 analog) mice. In a histopathologic analysis, the amounts of orthodontic tooth movement and numbers of osteoclasts were determined. The expression of mediators involved in bone remodeling was evaluated by real-time polymerase chain reaction.
  
  
  RESULTS
  Orthodontic tooth movement and the number of TRAP-positive cells were significantly decreased in CCR2(-/-) and P8A-treated mice in relation to wild-type and vehicle-treated mice, respectively. The expressions of RANKL, RANK, and osteoblasts markers (COL-1 and OCN) were lower in CCR2(-/-) than in wild-type mice. No significant difference was found in osteoprotegerin levels between the groups.
  
  
  CONCLUSIONS
  These data suggested a reduction of osteoclast and osteoblast activities in the absence of CCR2. The CCR2-CCL2 axis is positively associated with osteoclast recruitment, bone resorption, and orthodontic tooth movement. Therefore, blockage of the CCR2-CCL2 axis might be used in the future for modulating the extent of orthodontic tooth movement.
authors.affiliation: Laboratory of Immunopharmacology, Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvana Rodrigues de Albuquerque
authors.initials: SR
authors.lastname: Taddei
authors.forename: Ildeu
authors.initials: I
authors.lastname: Andrade
authors.forename: Celso Martins
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.forename: Thiago Pompermaier
authors.initials: TP
authors.lastname: Garlet
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Fernando de Queiroz
authors.initials: Fde Q
authors.lastname: Cunha
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Tarcília Aparecida
authors.initials: TA
authors.lastname: da Silva
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000473:pathology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D024042:Collagen Type I / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009969:Orthodontic Wires; D010006:Osteoblasts / Q000473:pathology; D015675:Osteocalcin / Q000032:analysis; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D054390:Receptors, CCR2 / Q000502:physiology*; D000071681:Tartrate-Resistant Acid Phosphatase; D014087:Tooth Movement Techniques / Q000295:instrumentation
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D024042:Collagen Type I; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D054390:Receptors, CCR2; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; D015675:Osteocalcin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase