Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
J Periodontal Res. 2011 Apr;46(2):246-51. doi: 10.1111/j.1600-0765.2010.01340.x. Epub 2011 Jan 18.
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.
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.
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.
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.
趋化因子可调节白细胞在牙周病中的迁移、募集和浸润。本研究旨在确定实验性口腔/局部趋化因子（C-C 基序）受体 2（CCR2）拮抗剂治疗对牙龈卟啉单胞菌诱导的牙周炎小鼠模型中牙槽骨丢失的影响。
Balb/C 小鼠（n=41）随机分为 4 组。第 1 组通过口腔/局部应用牙龈卟啉单胞菌感染 5 周。第 2 组也被感染，然后再用载剂（甲基纤维素水溶液）治疗 4 周。第 3 组被感染并接受 CCR2 拮抗剂（10mg/kg）的口腔/局部治疗。第 4 组作为未感染、未治疗的对照组。从感染的最后一天开始，小鼠接受 3 次腹腔注射钙黄绿素（30mg/kg）和茜素红（20mg/kg），以确定反映骨动态的矿化沉积。通过形态计量学和共聚焦荧光显微镜分析下颌骨。
使用 Tukey 检验比较各组间的牙槽骨丢失情况，并定性观察骨形成情况。与未感染的对照组动物相比，感染组的牙槽骨丢失明显更多（第 1 组比第 4 组，p<0.01）。载剂治疗的小鼠（第 2 组）显示出最大的牙槽骨丢失面积（p<0.01），而接受 CCR2 拮抗剂治疗的小鼠显示出最小的牙槽骨丢失面积，与对照组相似（第 3 组比第 4 组，p=0.14）。荧光染料摄取的定性分析表明，CCR2 拮抗剂治疗的小鼠骨形成增加，提示骨修复过程改善。
结果表明，CCR2 拮抗剂治疗抑制了该模型中的牙槽骨丢失并改善了骨形成。这些数据支持进一步评估 CCR2 拮抗剂作为治疗细菌诱导的牙槽骨吸收的新治疗方法的治疗靶点。
