The State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of stomatology, the First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, People's Republic of China.
J Periodontol. 2021 Jul;92(7):1036-1048. doi: 10.1002/JPER.19-0338. Epub 2020 Nov 13.
Occlusal trauma can aggravate periodontitis, but the mechanism remains unclear. Yes-associated protein (YAP), a mechanical stressor protein, may play an important role in this process.
Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the expression of YAP and inflammatory factors in patients with periodontitis accompanied with or without occlusal trauma. Through local administration of Porphyromonas gingivalis and composite resin bonding on maxillary molars in mice, we established periodontitis and occlusal trauma models. Treatment with or without XAV939, to inhibit YAP activation, was performed in these models. Micro-computed tomography, immunofluorescence (IF), and qRT-PCR were used to explore the YAP pathway in periodontitis with occlusal trauma. Cyclic stress and lipopolysaccharide (LPS) stimuli were applied to the L929 mouse fibroblast cell line with or without XAV939. Western blot, IF, and qRT-PCR were used to verify the in vivo results.
Activated dephosphorylated YAP and increased expression of inflammatory factors were observed in patients with periodontitis accompanied with occlusal trauma. In the mouse model of periodontitis with occlusal trauma, YAP transferred into the nucleus, resulting in Jun N-terminal kinases (JNK) related pro-inflammatory pathway up-regulation. L929 cell cyclic stress and LPS stimulation results confirmed the in vivo results. Application of XAV939 inhibited YAP protein dephosphorylation and reduced JNK pro-inflammatory pathway factor expression in vivo and in vitro.
Occlusal trauma can activate YAP nuclear transfer, resulting in the up-regulation of the JNK pro-inflammatory pathway. This can be inhibited by the XAV939 YAP inhibitor.
咬合创伤可加重牙周炎，但机制尚不清楚。Yes 相关蛋白（YAP）是一种机械应激蛋白，在这个过程中可能发挥重要作用。
采用 Western blot 和实时定量聚合酶链反应（qRT-PCR）检测伴或不伴咬合创伤的牙周炎患者中 YAP 和炎症因子的表达。通过在小鼠上颌磨牙局部给予牙龈卟啉单胞菌和复合树脂黏附，建立牙周炎和咬合创伤模型。在这些模型中，用或不用 XAV939（一种抑制 YAP 激活的药物）进行处理。采用 micro-CT、免疫荧光（IF）和 qRT-PCR 技术探讨咬合创伤伴牙周炎中 YAP 通路。将 LPS 刺激应用于 L929 小鼠成纤维细胞系，并用或不用 XAV939 处理。采用 Western blot、IF 和 qRT-PCR 验证体内结果。
伴咬合创伤的牙周炎患者中观察到磷酸化 YAP 激活和炎症因子表达增加。在咬合创伤伴牙周炎的小鼠模型中，YAP 转位入核，导致 Jun N-末端激酶（JNK）相关促炎途径上调。L929 细胞的循环应激和 LPS 刺激结果证实了体内结果。XAV939 的应用抑制了 YAP 蛋白去磷酸化，并减少了体内和体外 JNK 促炎途径因子的表达。
咬合创伤可激活 YAP 核转位，导致 JNK 促炎途径上调。这可以通过 XAV939 YAP 抑制剂来抑制。
