The inflammation-pyroptosis axis links local and systemic biomarker profiles to active alveolar bone microstructural...

This study aimed to identify biomarkers in saliva and serum that are highly correlated with the degree of bone destruction, and to further explore potential mechanisms, thereby providing evidence for accurate diagnosis and treatment of periodontitis.

A periodontitis model was established using maxillary molar ligation. Bone microstructural parameters were measured by Micro-CT. A multiplex liquid chip assay measured 21 biomarkers in saliva and serum, including inflammatory, oxidative stress, matrix-degrading, and bone remodeling factors. XGBoost was applied to select the key biomarkers, and we confirmed the findings with multiple linear regression and correlation tests. Histological assessments were performed to validate biomarker reliability and to investigate potential mechanisms.

Micro-CT showed significant differences in BV/TV, Tb.Sp, and CEJ-ABC among groups (P < 0.05); XGBoost identified monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and caspase-1 (CASP-1) as the main contributors. In saliva, these markers had fairly even contributions (27.7%, 34.4%, 18.4%); in serum, MCP-1 was the strongest (67.7%), followed by TNF-α (20.5%) and CASP-1 (8.4%). These key biomarkers correlated positively with Tb.Sp and CEJ-ABC, and they colocalized with gasdermin D (GSDMD) in areas of severe damage, which suggests a role in pyroptosis-related bone destruction.

Inflammatory signals in saliva and serum can reflect active destruction of alveolar bone micro-structure in periodontitis. The joint increase in key markers and their close location with GSDMD suggest that the mechanism may involve the pyroptosis pathway. These findings point to possible targets for treating periodontal bone loss and for managing the links between local bone damage and systemic diseases.