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.
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ABSTRACT: In this study, we first investigated the expressions of Jagged1, Notch2, the receptor activator of nuclear factor-kappa B ligand (RANKL), and interleukin (IL)-6 in areas of root resorption during experimental tooth movement in rats in vivo. We then assessed the effects of compression force (CF) with or without GSI (an inhibitor of Notch signaling) on Jagged1, RANKL, and IL-6 release from human periodontal ligament (hPDL) cells. Twelve male 6-wk-old Wistar rats were subjected to an orthodontic force of 50 g to induce mesially tipping movement of the upper first molars for 7 d. The expression levels of tartrate-resistant acid phosphatase, Jagged1, Notch2, IL-6, and RANKL proteins in the dental root were determined using an immunohistochemical analysis. Furthermore, the effects of the CF on Jagged1, IL-6, and RANKL production were investigated using hPDL cells in vitro. The effects of the cell-conditioned medium obtained from the hPDL cells subjected to CF (CFM) and Jagged 1 on osteoclastogenesis of human osteoclast precursor cells (hOCPs) were also investigated. Under the conditions of experimental tooth movement in vivo, resorption lacunae with multinucleated cells were observed in the 50 g group. In addition, immunoreactivity for Jagged1, Notch2, IL-6, and RANKL was detected on day 7 in the PDL tissue subjected to the orthodontic force. In the in vitro study, the compression force increased the production of Jagged1, IL-6, and RANKL from the hPDL cells, whereas treatment with GSI inhibited the production of these factors in vitro. The osteoclastogenesis increased with the CFM and rhJagged1, and the increase in the osteoclastogenesis was almost inhibited by GSI. These results suggest that the Notch signaling response to excessive orthodontic forces stimulates the process of root resorption via RANKL and IL-6 production from hPDL cells.Journal of Dental Research 11/2014; 94(1). DOI:10.1177/0022034514555364 · 4.14 Impact Factor
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ABSTRACT: Structured Abstract Objectives To investigate the effects of IL-17 on IL-6, IL-1β, and matrix metalloproteinase (MMP-1) production, and to compare the MMP-1 production between the individual and combined effects of IL-1β and IL-6 in human periodontal ligament fibroblasts (HPDLF). Materials and Methods Human periodontal ligament fibroblasts were cultured with IL-17 for 0.5, 1, 4, 24, 48, and 72 h, and were cultured with IL-1β, IL-6/sIL-6R, or a combination of IL-1β and IL-6/sIL-6R for 24 h. To measure the mRNA levels of IL-6, IL-1β, and MMP-1, total RNA was extracted from the cultured HPDLF, and a real-time PCR analysis was performed. The protein levels of IL-6, IL-1β, and MMP-1 in supernatants were measured using enzyme-linked immunosorbent assays (ELISAs). ResultsIL-17 significantly increased the expression of IL-6 and MMP-1 mRNA and protein, while IL-17 transiently increased the expression of IL-1β mRNA. The combination of IL-1β and IL-6/sIL-6R induced significantly higher levels of MMP-1 protein than IL-1β alone. ConclusionsIL-17 upregulated the production of IL-6 and MMP-1 sequentially in HPDLF. IL-6/sIL-6R may enhance the effects of IL-1β on MMP-1 production. The present results suggest that IL-17 induces MMP-1 production not only directly, but also indirectly by promoting IL-6 production, thus resulting in the degradation of collagens in the PDL.Orthodontics and Craniofacial Research 02/2014; 17(1). DOI:10.1111/ocr.12033 · 1.29 Impact Factor
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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.01/2012; 11(1). DOI:10.5466/ijoms.11.46