CCR2 deficiency results in increased osteolysis in experimental periapical lesions in mice.
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.
Garlet
Thiago Pompermaier
TP
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (FMRP/USP), Ribeirão Preto, SP, Brazil.
Fukada
Sandra Yasuyo
SY
Saconato
Isabella Francisco
IF
Avila-Campos
Mario Julio
MJ
da Silva
Tarcília Aparecida
TA
Garlet
Gustavo Pompermaier
GP
Cunha
Fernando de Queiroz
Fde Q
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
C515335:Ccr2 protein, mouse; D018925:Chemokines; D016207:Cytokines; D053245:RANK Ligand; D054390:Receptors, CCR2; C505689:Tnfsf11 protein, mouse