RGD Reference Report - Therapeutic effect of a topical CCR2 antagonist on induced alveolar bone loss in mice. - Rat Genome Database

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

Authors: Barros, SP  Arce, RM  Galloway, P  Lawter, R  Offenbacher, S 
Citation: Barros SP, etal., J Periodontal Res. 2011 Apr;46(2):246-51. doi: 10.1111/j.1600-0765.2010.01340.x. Epub 2011 Jan 18.
RGD ID: 8661687
Pubmed: (View Article at PubMed) PMID:21241302
DOI: Full-text: DOI:10.1111/j.1600-0765.2010.01340.x

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.

Disease Annotations    
Alveolar Bone Loss  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (chemokine (C-C motif) receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)

Additional Information