Circadian Disruption Exacerbates Periodontitis Progression Through Oxidative Stress Potentiation

The fast-paced lifestyles and shift work prevalent in modern society frequently disrupt circadian rhythms. Yet, the relationship between circadian regulation and periodontitis remains to be fully elucidated. Eighty male C57BL6 mice (6-8 weeks old) were randomly divided into circadian-normal (n=40) and circadian-disrupted (n=40) group. At week four, 30 circadian-normal mice were randomly selected as control (NC) for rhythm validation, while the remaining underwent ligature-induced periodontitis (NP). Similarly, 30 circadian-disrupted mice were designated as rhythm-disrupted control(RC) for model validation, with the remaining 10 receiving ligatures to establish periodontitis with concurrent circadian disruption (RP). The experimental protocols were approved by the Institutional Ethics Committee. To assess circadian disruption following altered light cycles, RNA was extracted from gingival tissues surrounding the second molars of NC and RC groups, followed by RT-PCR analysis of core clock gene rhythms. Results revealed dysregulated rhythms with varying magnitudes in light cycle-disrupted mice, confirming successful establishment of circadian disruption models. Micro-CT of mouse maxillae revealed increased cementoenamel junction-alveolar crest distances in RP group than NP, with immunohistochemistry showing elevated oxidative stress marker 8-OHdG. However, no significant changes were observed in the RC group compared to the NC . Although circadian disruption does not directly induce periodontitis, it exacerbates local reactive oxygen species (ROS) levels in periodontal tissues under inflammatory conditions. Targeting ROS clearance or circadian rhythm adjustment may thus serve as critical strategies to mitigate periodontitis with concurrent circadian dysregulation.