Investigation of circadian clock genes in the pathogenesis of periodontal disease

Investigation of Circadian Clock Genes in the Pathogenesis of Periodontal Disease Objective: The circadian rhythm regulates the physiological activities of tissues and cells. Disruptions in the circadian rhythm have been linked to diseases such as autoimmune disorders and cancer. This study aims to investigate the effects of periodontal disease on circadian rhythm by examining the gene and protein levels of circadian rhythm-related structures in the gingival tissue of individuals with similar sleep cycles but different periodontal diseases. Materials and Methods: The study included 60 systemically healthy, non-smoking individuals with similar sleep patterns but different periodontal diseases (periodontally healthy [n=20; 10 men and 10 women], gingivitis [n=20; 10 men and 10 women], periodontitis [n=20; 10 men and 10 women]). Gene and protein levels of circadian rhythm-related structures BMAL1, CLOCK, CRY1, CRY2, Per1, Per2, Per3, Rev-Erb-β, ROR-α in gingival samples were analyzed by Western Blot and RT-qPCR. Inflammation-related markers IL-1β, IL-6, TNF-α, NF-κB, IFN-γ, RANKL, and OPG were analyzed by RT-qPCR, and IL-1β and IL-6 protein levels by ELISA. Results: In periodontitis patients, CLOCK and Per3 gene and protein levels were significantly higher, while CRY1, CRY2, Per1, Per2, and Rev-Erb-β were lower (p<0.05). Inflammatory parameters IL-1β, IL-6, TNF-α, NF-κB, and IFN-γ were positively correlated with CLOCK and Per3, but they negatively correlated with CRY1, CRY2, Per1, Per2 and Rev-Erb-β (p <0.05). Conclusion: Periodontitis may disrupt the circadian rhythm by altering circadian clock gene and protein expression in the gingiva. Circadian clock genes may interact with inflammatory processes in periodontal diseases. Keywords: Circadian Rhythm, Clock Genes, CRY1, Inflammation, Per1, Periodontitis