title: CCR2 deficiency results in increased osteolysis in experimental periapical lesions in mice.
abstract: BACKGROUND
  Periapical lesions are chronic inflammatory disorders of periradicular tissues caused by etiologic agents of endodontic origin. The inflammatory chemokines are thought to be involved in the latter observed osteolysis. With a murine model of experimental periapical lesion, the objective of this study was to evaluate the role of the chemokine receptor CCR2 in the lesion progression, osteoclast differentiation and activation, and expression of inflammatory osteolysis-related mediators.
  
  
  METHODS
  For lesion induction, right mandibular first molars were opened surgically with a 1/4 carbine bur, and 4 bacterial strains were inoculated in the exposed dental pulp; left mandibular first molars were used as controls. Animals were killed at 3, 7, 14, and 21 days after surgeries to evaluate the kinetics of lesion development.
  
  
  RESULTS
  CCR2 KO mice showed wider lesions than WT mice. CCR2 KO mice also expressed higher levels of the osteoclastogenic and osteolytic factors, receptor activator of nuclear factor kappa B ligand (RANKL) and cathepsin K, of the proinflammatory cytokine tumor necrosis factor-alpha, and of the neutrophil migration related chemokine, KC.
  
  
  CONCLUSIONS
  These results suggest that CCR2 is important in host protection to periapical osteolysis.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (FMRP/USP), Ribeirão Preto, SP, Brazil.
authors.forename: Thiago Pompermaier
authors.initials: TP
authors.lastname: Garlet
authors.forename: Sandra Yasuyo
authors.initials: SY
authors.lastname: Fukada
authors.forename: Isabella Francisco
authors.initials: IF
authors.lastname: Saconato
authors.forename: Mario Julio
authors.initials: MJ
authors.lastname: Avila-Campos
authors.forename: Tarcília Aparecida
authors.initials: TA
authors.lastname: da Silva
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Fernando de Queiroz
authors.initials: Fde Q
authors.lastname: Cunha
mesh_terms: D016301:Alveolar Bone Loss / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D008137:Longitudinal Studies; D008334:Mandible; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008963:Molar; D010010:Osteoclasts / Q000276:immunology* / Q000502:physiology; D010483:Periapical Diseases / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D053245:RANK Ligand / Q000276:immunology / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: C515335:Ccr2 protein, mouse; D018925:Chemokines; D016207:Cytokines; D053245:RANK Ligand; D054390:Receptors, CCR2; C505689:Tnfsf11 protein, mouse