T-helper 17 cells mediate the osteo/odontoclastogenesis induced by excessive orthodontic forces

Department of Orthodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Oral Diseases (Impact Factor: 2.43). 12/2011; 18(4):375-88. DOI: 10.1111/j.1601-0825.2011.01886.x
Source: PubMed


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.

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    • "OIIRR is an extremely complex, sterile inflammatory process that involves various disparate components including mechanical force, teeth, bone, different types of cells, the surrounding matrix, and certain biological messengers.1,8 With regard to the relationship between OIIRR and IL-6, Hayashi et al.9 indicated that IL-6 is important for the induction and further processing of mechanically induced root resorption in rats. Yamaguchi et al.10 reported that stimulation with substance P increases the level of IL-6 in dental pulp fibroblasts obtained from patients with severe root resorption. "
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    ABSTRACT: To determine the interleukin (IL)-6 levels in gingival crevicular fluid (GCF) of patients with severe root resorption after orthodontic treatment and investigate the effects of different static compressive forces (CFs) on IL-6 production by human periodontal ligament (hPDL) cells and the influence of IL-6 on osteoclastic activation from human osteoclastic precursor (hOCP) cells in vitro. IL-6 levels in GCF samples collected from 20 patients (15 and 5 subjects without and with radiographic evidence of severe root resorption, respectively) who had undergone orthodontic treatment were measured by ELISA. The levels of IL-6 mRNA in hPDL cells and IL-6 protein in conditioned medium after the application of different uniform CFs (0, 1.0, 2.0, or 4.0 g/cm(2) for up to 72 h) were measured by real-time PCR and ELISA, respectively. Finally, the influence of IL-6 on mature osteoclasts was investigated by using hOCP cells on dentin slices in a pit-formation assay. Clinically, the IL-6 levels were significantly higher in the resorption group than in the control group. In vitro, IL-6 mRNA expression significantly increased with increasing CF. IL-6 protein secretion also increased in a time- and magnitude-dependent manner. Resorbed areas on dentin slices were significantly greater in the recombinant human IL-6-treated group and group cultured in hPDL cell-conditioned medium with CF application (4.0 g/cm(2)) than in the group cultured in hPDL cell-conditioned medium without CF application. IL-6 may play an important role in inducing or facilitating orthodontically induced inflammatory root resorption.
    Full-text · Article · Dec 2013 · Korean Journal of Orthodontics
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    • "Interleukin-6 (IL-6) is a potent stimulus for bone resorption and osteoclastic cell recruitment during orthodontic tooth movement [3] [4]. 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 [5]. Yamaguchi et al. reported that Stimulation with substance P increased the levels of IL-6 in obtained from patient with severe root resorption [6]. "
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    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.
    Full-text · Article · Jan 2012
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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.
    No preview · Article · Sep 2012 · Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie
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