The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

Abstract

This study aimed to investigate the relationship between inflammation‐related T‐helper cell polarization and the receptor activator for nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, which is associated with bone resorption or remodeling of chronic periodontitis patients. Gingival crevicular fluid (GCF) and gingival tissues were obtained from periodontally healthy individuals (PH group) and chronic periodontitis patients (CP group). The GCF levels of IFN‐γ, IL‐4, IL‐17, and IL‐10 linked to T‐helper cell polarization toward the Th1, Th2, Th17, and Treg phenotypes, respectively, were determined by ELISA. The expression levels of these cytokines and the polarized T‐helper cells in gingival tissues were assessed through immunohistochemical and immunofluorescence assays. In addition, the RANKL and OPG expression levels in gingival tissues were detected by immunohistochemical assays, and linear regression analysis was used to identify the potential relationship between T‐helper cell polarization and the RANKL/OPG ratio. In total, 22 individuals and 35 patients were enrolled in the present study. In both GCF and gingival tissues, increased levels of IL‐17 and the decreased levels of IL‐4 and IL‐10 were observed in the CP group. When polarized T‐helper cells were identified in gingival tissues, more Th1 and Th17 cells were found in the CP group, whereas more Th2 and Treg cells were found in the PH group. Although there was no significant difference in OPG expression between the two groups, the RANKL/OPG ratio in the CP group was higher than that in the PH group. The linear regression analysis showed that the presence of more Th1 and Th17 cells correlated with a higher RANKL/OPG ratio, whereas the presence of more Th2 cells correlated with a lower RANKL/OPG ratio. Th1 and Th17 cells are positively correlated and Th2 cells are negatively correlated with the RANKL/OPG ratio. Our data suggest that T‐helper cell polarization is closely linked to the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients.

Determinants of Periodontal/Periapical Lesion Stability and Progression

“…The pressure side, characterized by bone resorption, displays a high RANKL/OPG profile similar to that observed in chronic periodontitis, whereas the tension side, characterized by new bone formation, presents a RANKL < OPG profile similar to gingivitis sites (Menezes et al 2008). Accordingly, previous studies also described an increased RANKL/OPG ratio in periodontitis samples in comparison to healthy or gingivitis tissues, with increased RANKL levels associated with progressive tissue destruction (Bostanci et al 2007; Bi, Sun, et al 2019; Lopez Roldan et al 2020). Nevertheless, longitudinal prospective studies are required to further determine if a RANKL/OPG ratio comprises an effective biomarker of disease activity as described for other bone-related conditions.…”

“…Indeed, while IFN-γ and IL17 can amplify host response by the induction of proinflammatory cytokines and mediate RANKL production by resident cells of periapical lesions, Th1 and Th17 responses can be mutually inhibitory (Colavite et al 2019; Duka et al 2019). In contrast, the simultaneous detection of high levels of both IL17 and IFN-γ in diseased periodontium is also described, suggesting a possible interplay toward disease progression (Dutzan, Gamonal, et al 2009; Bi, Sun, et al 2019; Sommer et al 2019). Considering that even cytokines that are routinely used as Th polarization surrogates (i.e., IFN-γ, IL17) can also be produced by other cell types and that Th plasticity has been described in periodontal tissues (with the occurrence of Tbet + IL10 + and FOXp3 + IL17 + cells) (Okui et al 2012), it becomes clear that comprehensive studies, not exclusively focused on a single mediator or cell subset, are required to unravel the immunological complexity underlying lesion progression.…”

Effects of melatonin on insulin signaling and inflammatory pathways of rats with apical periodontitis

“…2019) and lower concentrations of the anti‐inflammatory cytokine, IL‐10 (Bi et al . 2019). Hoppe et al .…”

Maintaining homeostatic control of periodontal bone tissue

“…258,259 Bi et al reported increased T H 1/T H 17 cells in periodontitis-afflicted gingival isolates, whereas T H 2/T regulatory cells were upregulated in healthy gingiva. 260 Serotype b of A. actinomycetemcomitans induced elevated T-bet + interferon-gamma + and RAR-related orphan receptor gamma t + interleukin-17 + T cells in periodontal lesions, which were associated with increased RANKL and alveolar bone resorption. 258 Capsular-defective mutant strains of P. gingivalis promoted less bone loss and decreased T H 1/T H 17 cells and related cytokines compared with the encapsulated W50 wild-type strain.…”

“…Monasterio and coworkers recently employed the murine oral inoculation periodontitis model to show that the T H 1/T H 17 immune response and periodontal bone loss is strain dependent 258,259 . Bi et al reported increased T H 1/T H 17 cells in periodontitis‐afflicted gingival isolates, whereas T H 2/T regulatory cells were upregulated in healthy gingiva 260 . Serotype b of A. actinomycetemcomitans induced elevated T‐bet + interferon‐gamma + and RAR‐related orphan receptor gamma t + interleukin‐17 + T cells in periodontal lesions, which were associated with increased RANKL and alveolar bone resorption 258 .…”