State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases and Department of Preventive Dentistry, National Center of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Periodontal Res. 2022 Dec;57(6):1183-1197. doi: 10.1111/jre.13055. Epub 2022 Sep 22.
Pyroptosis has both a caspase-1-dependent canonical pathway and a caspase-4/-5/-11-dependent noncanonical pathway. They play an important role in inflammatory damage and related diseases. Canonical pyroptosis was reported to be involved in periodontitis. However, knowledge of caspase-4/-5/-11-dependent noncanonical pathway involvement remains limited. The aim of this study was to investigate the outcomes of pyroptosis inhibition on periodontitis as well as the possible mechanism, in order to provide a potential target for alleviating periodontitis.
Human and rat periodontitis tissues were collected for immunohistochemistry (IHC). Micro-computed tomography was used to assess alveolar bone loss in experimental periodontitis model. Pyroptosis-related proteins were tested by western blot. propidium iodide staining and lactate dehydrogenase release were used to verify pyroptosis activation. RNA sequencing was applied to investigate the preliminary mechanism of the reduced periodontal inflammation induced by YVAD-CHO.
Both canonical- and noncanonical-related proteins were detected in human and rat periodontitis tissue. The pyroptosis-inhibited group demonstrated less inflammatory response and bone absorption. In vitro, pyroptosis was activated by lipopolysaccharide and inhibited by YVAD-CHO. RNA sequencing demonstrated that the expression of A20 and IκB-ζ was increased and verified by western blot in vitro and IHC in vivo.
These results suggest that inhibition of pyroptosis-reduced inflammation and alveolar bone resorption in periodontitis.
细胞焦亡有依赖于半胱天冬酶-1 的经典途径和依赖于半胱天冬酶-4/-5/-11 的非经典途径。它们在炎症损伤和相关疾病中发挥重要作用。经典细胞焦亡被报道与牙周炎有关。然而，关于半胱天冬酶-4/-5/-11 依赖性非经典途径的参与仍知之甚少。本研究旨在探讨细胞焦亡抑制对牙周炎的影响及可能的机制，为缓解牙周炎提供潜在靶点。
收集人牙周炎和大鼠牙周炎组织进行免疫组织化学（IHC）检测。采用微计算机断层扫描评估实验性牙周炎模型中的牙槽骨丧失。通过蛋白质印迹检测细胞焦亡相关蛋白。碘化丙啶染色和乳酸脱氢酶释放用于验证细胞焦亡的激活。RNA 测序用于研究 YVAD-CHO 减轻牙周炎症的初步机制。
在人牙周炎和大鼠牙周炎组织中均检测到经典途径和非经典途径相关蛋白。细胞焦亡抑制组炎症反应和骨吸收减少。体外实验中，脂多糖激活细胞焦亡，而 YVAD-CHO 抑制细胞焦亡。RNA 测序显示，A20 和 IκB-ζ 的表达增加，并通过体外蛋白质印迹和体内 IHC 验证。
这些结果表明，抑制细胞焦亡可减轻牙周炎中的炎症和牙槽骨吸收。
