T-helper 17 cells mediate the osteo/odontoclastogenesis induced by excessive orthodontic forces
ABSTRACT The aim of this study was to investigate how T-helper 17 cells (Th17 cells), interleukin (IL)-17, and interleukin-6 contribute to root resorption during orthodontic tooth movement.
Fifteen male 6-week-old Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. The expression levels of TRAP, IL-17, the IL-17 receptor (IL-17R), and IL-6 proteins were determined in periodontal ligament (PDL) by immunohistochemical analysis. Moreover, the fluorescent localization immunoassay was performed to detect Th17 cells. Furthermore, the effects of IL-17 on IL-6 release were investigated using human PDL cells in vitro. The effect of IL-17 on osteoclastogenesis was evaluated by TRAP staining, actin ring staining, and the pit formation assay.
The immunoreactivity for Th17, IL-17, IL-17R, and IL-6 was detected in PDL tissue subjected to the orthodontic force on day 7. IL-17 increased the release of IL-6 from human periodontal ligament cells in a time-dependent manner. Moreover, IL-17 stimulated osteoclastogenesis from human osteoclast precursor cells, and these effects were partially suppressed by an anti-IL-6 antibody.
These results suggest that Th17 cells may aggravate the process of orthodontically induced inflammatory root resorption.
- SourceAvailable from: Kazutaka Kasai
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- "Interleukin-6 (IL-6) is a potent stimulus for bone resorption and osteoclastic cell recruitment during orthodontic tooth movement  . With regard to the relationship between EARR and IL-6, Hayashi et al. indicated that IL-6 is important for the induction and further processing of mechanically-induced root resorption in the rat . Yamaguchi et al. reported that Stimulation with substance P increased the levels of IL-6 in obtained from patient with severe root resorption . "
ABSTRACT: The aim of this study was to investigate the amount of external apical root resorption (EARR) and the re-lease of interleukin (IL)-6 in the gingival crevicular fluid (GCF) in subjects treated with a low-force low-friction system. Sixty patients were assigned to two groups of thirty patients for each: one group re-ceived treatment with self-ligating brackets and the other with conventional ligated edgewise brackets. All patients were treated with extraction of the maxillary first premolars. The EARR of the maxillary central incisors was evaluated on the periapical radiographs and cephalograms, taken before and after orthodon-tic treatment. The GCF was also collected non-inva-sively from the mesial and distal sides of central inci-sors by using filter paper strips before and after or-thodontic treatment. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the IL-6 levels in the GCF samples. A significant difference was found in the amount of EARR between the pa-tients with self-ligating brackets and conventional brackets. The mean amount of EARR was signifi-cantly lower for self-ligating brackets than conven-tional brackets (p < 0.05). The GCF levels of IL-6 for the patients with self-ligating brackets appliance were significantly lower than for those with the conven-tional brackets (p < 0.05). These results show that the mean amount of EARR and the GCF levels of IL-6 were significantly lower in the patients treated using low-force low-friction appliances than conventional brackets. Therefore, self-ligating brackets may be a useful system for reducing inflammation and EARR.01/2012; 11(1). DOI:10.5466/ijoms.11.46
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ABSTRACT: Background and objective Orthodontic tooth movement is known to cause sterile inflammation of the periodontal ligament (PDL). It may also be accompanied by pathological effects of external apical root resorption, with interindividual differences in the incidence and extent of resorption. An involvement of autoimmunological mechanisms is currently under discussion. This study aimed to improve our understanding of similarities between the inflammatory mechanisms underlying the pathophysiology of periodontitis and root resorption. Materials and methods Human PDL cells were stimulated with interleukin (IL)-1β/IL-17A/IFN-γ, or left non-stimulated. Their potential for phagocytosis was then evaluated by incubation with dextran or E. coli or S. aureus particles, followed by flow cytometric and immunohistochemical analysis. Real-time polymerase chain reaction (PCR) was used to analyze receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) expression in PDL cells. Verification was obtained in vivo by studying IL-17A, RANKL, and OPG expression in biopsies of inflamed periodontal tissues and in biopsies of rat maxillae with mechanically induced root resorption. Statistical analysis included Wilcoxon’s rank sum test to analyze gene expression data and one-way ANOVA in conjunction with Tukey’s post hoc test to analyze flow cytometric data. Results PDL cells phagocytosed foreign particles under both inflammatory and non-inflammatory conditions. Furthermore, IL-17A significantly downregulated RANKL expression while significantly upregulating OPG expression in PDL cells. These immunomodulatory cytokines were also demonstrable in both inflammatorily altered periodontal tissues and root resorption lacunae, while the incidence of IL-7A was strikingly variable in resorption areas. Conclusion PDL cells were demonstrated to effect phagocytosis and to express immunomodulatory molecules, which proves their capability of participating in periodontal osteoimmunological processes. The development of root resorption and periodontitis appears to be governed by similar pathophysiological mechanisms.Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie 09/2012; 73(6). DOI:10.1007/s00056-012-0102-3 · 0.82 Impact Factor
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ABSTRACT: OBJECTIVE: The aim of this study was to investigate how atopic dermatitis (AD) contributes to root resorption during orthodontic tooth movement. MATERIALS AND METHODS: Atopic dermatitis model mice and wild-type mice were subjected to an excessive orthodontic force (OF) to induce movement of the upper first molars. The expression levels of the tartrate-resistant acid phosphatase (TRAP), IL-17, IL-6, and RANKL proteins were determined in the periodontal ligament (PDL) by an immunohistochemical analysis. Furthermore, the effects of the compression force on co-cultures of CD4(+) cells from AD patients or healthy individuals and human PDL cells were investigated with regard to the levels of secretion and mRNA expression of IL-17, IL-6, RANKL, and osteoprotegerin. RESULTS: The immunoreactivities for TRAP, IL-17, IL-6, and RANKL in the AD group were found to be significantly increased. The double immunofluorescence analysis for IL-17/CD4 detected immunoreaction. The secretion of IL-17, IL-6, and RANKL, and the mRNA levels of IL-6 and RANKL in the AD patients were increased compared with those in healthy individuals. CONCLUSION: Th17 cells may therefore be associated with the deterioration of root resorption of AD mice, and may explain why AD patients are more susceptible to root resorption than healthy individuals when an excessive OF is applied.Oral Diseases 12/2012; 19(7). DOI:10.1111/odi.12053 · 2.40 Impact Factor