Abstract
BACKGROUND: Periodontitis and diabetes are chronic diseases where inflammation plays a central role, with each condition exacerbating the other. Pyroptosis, an inflammatory form of programmed cell death, is implicated in periodontitis and diabetes. The activation of gasdermin D (GSDMD), a key mediator of pyroptosis, promotes cytokine release and perpetuates tissue destruction in both. However, the role of the noncanonical pyroptosis pathway mediated by caspase 4 (CASP4) remains less understood. The study aimed to determine the gene expression of noncanonical pyroptosis biomarkers CASP4 and GSDMD in periodontitis and diabetes individuals and correlate with the periodontal and diabetic parameters. MATERIALS AND METHODS: Sixty individuals were recruited and divided into four groups: Group 1 (healthy), Group 2 (periodontitis), Group 3 (diabetes), and Group 4 (periodontitis with diabetes). Gingival tissue samples were collected from all groups, and the relative mRNA expression levels of CASP4 and GSDMD were determined using reverse transcription polymerase chain reaction. The correlation between CASP4 and GSDMD expression and periodontal parameters - plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL), as well as diabetic parameters - fasting blood sugar and glycated hemoglobin (HbA1C) was analyzed. RESULTS: The relative mRNA expression of CASP4 and GSDMD was highest in Group 4 and lowest in Group 1. Statistical significance was observed between the groups (P ≤ 0.05) for CASP4 and GSDMD. A significant positive correlation was found between CASP4 and GSDMD expression and periodontal parameters (PI, GI, PPD, and CAL), as well as the diabetic parameter HbA1C (P ≤ 0.01). CONCLUSIONS: High expression of CASP4 and GSDMD was present in the gingiva of periodontitis and diabetes individuals and correlated with the diabetic and periodontal clinical parameters. This suggests that noncanonical pyroptosis contributes to periodontitis and diabetes pathogenesis through the CASP4/GSDMD axis. The inhibition of GSDMD offers a promising therapeutic approach in managing periodontitis and diabetes.