CCR2 Deficiency Results in Increased Osteolysis in Experimental Periapical Lesions in Mice

• Published in: Journal of endodontics Vol. 36; no. 2; pp. 244 - 250
• Main Authors: Garlet, Thiago Pompermaier, DDS, MS, Fukada, Sandra Yasuyo, DDS, PhD, Saconato, Isabella Francisco, PharmD, Avila-Campos, Mario Julio, PhD, Aparecida da Silva, Tarcília, DDS, PhD, Garlet, Gustavo Pompermaier, DDS, PhD, de Queiroz Cunha, Fernando, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2010
• Subjects: Alveolar Bone Loss - complications; Alveolar Bone Loss - immunology; Alveolar Bone Loss - metabolism; Analysis of Variance; Animals; Bone resorption; CCR2; chemokine receptors; Chemokines - immunology; Chemokines - metabolism; Cytokines - immunology; Cytokines - metabolism; Dentistry; Disease Models, Animal; Endocrinology & Metabolism; Longitudinal Studies; Mandible; Mice; Mice, Inbred C57BL; Mice, Knockout; Molar; OPG; Osteoclasts - immunology; Osteoclasts - physiology; Periapical Diseases - complications; Periapical Diseases - immunology; Periapical Diseases - metabolism; periapical lesions; RANK Ligand - immunology; RANK Ligand - metabolism; RANKL; Receptors, CCR2 - genetics; Receptors, CCR2 - immunology; Receptors, CCR2 - physiology; Severity of Illness Index; Statistics, Nonparametric; Bone resorption; periapical lesions; chemokine receptors; RANKL; OPG; CCR2
• ISSN: 0099-2399; 1878-3554
• DOI: 10.1016/j.joen.2009.09.004

Abstract Introduction 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 ¼ 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.