MOLECULAR MECHANISMS OF DIABETIC PERIODONTITIS: IDENTIFICATION OF KEY OXIDATIVE STRESS-RELATED GENES AND POTENTIAL THERAPEUTIC ROLE OF METFORMIN THROUGH MMP14 AND PXDN.

AIM: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship, with oxidative stress potentially serving as a crucial pathological bridge. However, the underlying molecular mechanisms remain unclear.

METHODS

We identified differentially expressed genes (DEGs) related to oxidative stress in periodontitis and diabetes. Consensus clustering was performed to identify disease subtypes. Machine learning algorithms, including Support Vector Machine, LASSO regression, and Random Forest, were employed to identify key regulatory genes. Molecular docking was conducted to explore the potential interaction between metformin and target proteins.

RESULTS

We identified 17 overlapping genes associated with oxidative stress, diabetes, and periodontitis. Two distinct molecular subtypes were identified with significant differences in immune cell infiltration patterns. Four key genes (FOS, MMP14, CD38, and PXDN) were identified as potential therapeutic targets. The nomogram based on these four genes showed excellent diagnostic performance (AUC=0.931). Molecular docking analysis revealed strong binding affinities between metformin and two targets (MMP14: -5.6 kcal/mol; PXDN: -5.2 kcal/mol).

CONCLUSIONS

Our study provides novel insights into the molecular mechanisms linking periodontitis and diabetes through oxidative stress, identifying potential therapeutic targets and suggesting a possible mechanism for metformin's therapeutic effects in diabetic periodontitis.