Therapeutic effect of a topical CCR2 antagonist on induced alveolar bone loss in mice.

BACKGROUND AND

OBJECTIVE

Chemokines are known to regulate leukocyte trafficking, recruitment and infiltration in periodontal diseases. The study objective was to determine the effect of an experimental oral/topical chemokine (C-C motif) receptor 2 (CCR2)-antagonist treatment on alveolar bone loss in a mouse model of Porphyromonas gingivalis-induced periodontitis.

MATERIAL AND

METHODS

Balb/C mice (n = 41) were randomly assigned to four groups. Group 1 was infected by P. gingivalis applied orally/topically for 5 wk. Group 2 was also infected and then treated with vehicle (aqueous methylcellulose) for an additional 4 wk. Group 3 was infected and orally/topically treated with CCR2 antagonist (10 mg/kg). Group 4 served as a noninfected, nontreated control group. Mice received intraperitoneal injections of Alizarin (30 mg/kg) and calcein (20 mg/kg) three times from the last day of infection to determine mineral deposition, reflecting bone dynamics. Mandibles were analysed by morphometry and confocal fluorescence microscopy.

RESULTS

Alveolar bone loss was compared among groups using Tukey's test, and bone formation was qualitatively observed. Infected mice showed significantly greater alveolar bone loss than noninfected control animals (group 1 vs. 4, p < 0.01). Vehicle-treated mice (group 2) showed the largest area of alveolar bone loss (p < 0.01), while mice treated with the CCR2 antagonist showed the smallest area of alveolar bone loss and were similar to the control group (group 3 vs. 4, p = 0.14). Qualitative analysis of fluorescent dye uptake indicated increased bone formation in CCR2-antagonist-treated mice, suggesting an improved bone repairing process.

CONCLUSION

The results suggested that treatment with CCR2 antagonist inhibited alveolar bone loss and improved bone formation in this model. These data support further evaluation of CCR2 antagonist as a therapeutic target for the development of new treatment modalities on bacterially induced alveolar bone resorption.