title: Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling.
abstract: Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Huaixiu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Medical Engineering, The Second Artillery General Hospital PLA, Beijing, China.
authors.forename: Minguang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Shisen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010518:Periodontitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013315:Stress, Psychological
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha