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Inhibition of yes‐associated protein dephosphorylation prevents aggravated periodontitis with occlusal trauma
Author(s) -
Wei Wei,
Xue Lili,
Tan Liangyu,
Liu Jie,
Yang Qin,
Wang Jiajia,
Yan Bing,
Cai Qiaoling,
Yang Li,
Yue Yuan,
Hao Liang,
Wang Min,
Li Jinle
Publication year - 2021
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1002/jper.19-0338
Subject(s) - periodontitis , porphyromonas gingivalis , western blot , in vivo , lipopolysaccharide , molar , dephosphorylation , dentistry , medicine , phosphorylation , chemistry , microbiology and biotechnology , pathology , immunology , biology , phosphatase , biochemistry , gene
Abstract Background 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. Methods 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. 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 . Conclusions 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.