Lu Huaixiu, Xu Minguang, Wang Feng, Liu Shisen, Gu Jing, Lin Songshan, Zhao Lisheng
Department of Stomatology, Navy General Hospital, Beijing, China.
Department of Medical Engineering, The Second Artillery General Hospital PLA, Beijing, China.
Exp Mol Med. 2016 Mar 25;48(3):e223. doi: 10.1038/emm.2015.127.
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.
牙周炎是一种常见的慢性炎症性疾病。最近的研究表明，慢性应激（CS）可能会调节牙周疾病，但CS诱导的牙周炎模型很少，其潜在机制尚不清楚。本研究建立了一种由尼龙线结扎诱导的与CS相关的大鼠牙周炎模型。通过影像学和病理学检查评估该模型中牙周炎的严重程度。通过酶联免疫吸附测定法评估血清白细胞介素（IL）-1β、IL-6和IL-8水平升高所表明的炎症反应。通过逆转录聚合酶链反应和蛋白质印迹法检测Toll样受体4（TLR4）和糖皮质激素受体-α（GR-α）的表达。采用旷场试验和血清皮质酮来评估CS。结果表明，CS诱导了牙周炎动物的行为变化并增加了皮质酮水平。CS刺激显著增加了牙槽骨吸收、牙周袋深度和菌斑数量。它还增强了炎症反应。这些结果表明，CS加速了结扎诱导的与牙周炎相关的病理变化。对相关机制的进一步分析表明，在接受CS的动物的牙周组织中，GR-α表达显著下调。在体外对脂多糖和皮质类固醇处理的人牙周膜成纤维细胞中阻断GR-α信号通路可显著上调p-Akt（蛋白激酶B）和TLR4的表达，促进核因子-κB活性并增加IL-1β、IL-6和IL-8的水平。本研究表明，CS可能通过GR-α信号介导的炎症反应加速牙周炎的病理进展，这可能是治疗牙周疾病，特别是CS患者的潜在治疗靶点。
