Circadian disruption by simulated shift work aggravates periodontitis via orchestrating BMAL1 and GSDMD-mediated pyroptosis  

作　　者：Yazheng Wang Rui Li Qingyuan Ye Dongdong Fei Xige Zhang Junling Huang Tingjie Liu Jinjin Wang Qintao Wang 

机构地区：[1]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Periodontology,School of Stomatology,the Fourth Military Medical University,Xi’an,China [2]Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,Department of Periodontology,College of Stomatology,Xi’an Jiaotong University,Xi’an,China [3]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi Key Laboratory of Stomatology,Digital Dentistry Center,School of Stomatology,the Fourth Military Medical University,Xi’an,China [4]Department of Stomatology,the Seventh Medical Center of PLA General Hospital,Beijing,China

出　　处：《International Journal of Oral Science》2025年第1期122-132,共11页国际口腔科学杂志(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.82170955,82101064);the Xinfei Program funded by Fourth Military Medical University。

摘　　要：Approximately 20%to 30%of the global workforce is engaged in shift work.As a significant cause of circadian disruption,shift work is closely associated with an increased risk for periodontitis.Nevertheless,how shift work-related circadian disruption functions in periodontitis remains unknown.Herein,we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis.RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1(BMAL1)and activation of the Gasdermin D(GSDMD)-mediated pyroptosis were involved in the pathogenesis of that.Mechanically,BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3(NLRP3)inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1(NR1D1),and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter.GSDMD-mediated pyroptosis accelerated periodontitis progression,whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity.And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis.These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.

关 键 词：BMAL1 NLRP3 PERIOD 

分 类 号：R36[医药卫生—病理学]