CCL2/CCR2 signaling activation contributes to tooth movement pain
10.3760/cma.j.issn.1002-0098.2014.08.012
- VernacularTitle:趋化因子CCL2/受体CCR2信号轴激活调控正畸牙移动疼痛的实验研究
- Author:
Zhi YANG
1
;
Wei LUO
;
Runqing FU
;
Yu TAN
;
Lingjun YUAN
;
Bing FANG
Author Information
1. 200011,上海交通大学医学院附属第九人民医院口腔医学院口腔颅颌面科上海市口腔医学研究所上海市口腔医学重点实验室
- Keywords:
Chemokine CCL2;
Receptors,CCR2;
Tooth movement;
Signal transduction
- From:
Chinese Journal of Stomatology
2014;49(8):500-505
- CountryChina
- Language:Chinese
-
Abstract:
Objective To test the hypothesis that the CCL2/CCR2 signaling pathway plays an important role in pain induced by experimental tooth movement.Methods Male Sprague-Dawley rats weighing between 200 and 300 g were used in this study.Expression of CCL2/CCR2 in the trigeminal ganglion(TG) was determined by Western blotting 0 h,4 h,1 d,3 d,5 d,7 d after tooth movement.Localization of the CCL2 was revealed by immunohistochemistry.Changes in body weight,nocifensive behaviors,and the effects of CCL2/CCR2 antagonists on these changes in pain behaviors were evaluated.Exogenous CCL2 was injected into periodontal tissues and added to TG neurons in culture and the resulting c-fos expression and pain responses were detected.In addition,the expression and cellular localization of CCL2 in the medullary dorsal horn (MDH) was determined by immunohistochemistry 3 d and 14 d after tooth movement.Results Experimental tooth movement led to a statistically significant increase in CCL2/CCR2 expression at the protein level from day 3 to 7 after application of force initiating tooth movement.When compared with control group(1.000± 0.000),CCL2 increased to (2.620 ± 0.128),(3.300±0.197) and (1.740±1.290) at day 3,5 and 7 respectively,which were statistically significant (P＜0.05).CCR2 expression levels were (1.636±0.061) and (1.766±0.126) compared with that in control group (1.000±0.000) at day 3 and 5 respectively with statistical significance (P＜0.05).Both of them peaked on day 5 (3.3 and 1.8 time compared to control group).Application of recombinant CCL2 led to the up-regulation of c-fos expression in vivo and in vitro,and triggered a corresponding nocifensive behavior in rats.The magnitude of the nocifensive behavior could be reduced by a CCR2 antagonist,and by CCL2 neutralizing antibody.Furthermore,we found a significant increase in the expression of CCL2,corresponding well to the upregulation of the time spent on nocifensive behaviors after ETM.In addition,CCL2 was up-regulated in TG neurons and astrocytes in Vc.Conclusions The CCL2/CCR2 axis was modulated by experimental tooth movement and involved in the development of tooth movement pain,and thus palyed an important role in orthodontic pain mechanism.
