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.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

The purpose of the study was to investigate the influencing factors of mortality rate in the bone marrow transplantation in mice. The recipient mice receiving whole-body irradiation of gamma-ray were infused with the same strain of bone marrow cells or the mixture of the bone marrow cells and splenocytes respectively. Experiments were carried out in four batches, with different strains of mice used, respectively. The manifestations and the appearance of graft-versus-host disease (GVHD) were observed, as well as the mortality rate within 35 d of the transplantation in the recipient mice. The mortality rate of the first group of recipient mice was the lowest, the mortality rate of the second group of recipient mice was the highest and the obvious GVHD performance was observed before death. In the third group, the mortality rate declined and there was statistical significance compared to that of the second group. The mortality rate of the fourth group of mice was higher than that of the third group, but still lower than that of the second group of mice and there is a statistical significance. This evidence suggested that mouse genetic purity, splenocytes, the ratio of the bone marrow cells and splenocytes and the week-old of the mouse could be the important influencing factors of the mortality rate in mouse bone marrow transplantation.
Animals ; Bone Marrow Transplantation ; adverse effects ; methods ; mortality ; Cell Transplantation ; Female ; Graft vs Host Disease ; immunology ; mortality ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Mice, Transgenic ; Spleen ; cytology ; Survival Rate ; Whole-Body Irradiation