Signal-Transducing Adaptor Proteins in Periodontal Disease

Signal-transducing adaptor proteins (STAPs), particularly STAP-1 and STAP-2, are involved in intracellular signaling pathways that regulate cell growth, immune responses, and inflammatory processes, and have been implicated in the pathogenesis of several chronic inflammatory and malignant conditions. Their regulatory partners, STAT3 and STAT5A, are transcription factors known to modulate immune and inflammatory signaling, while NLRP3 (a key component of the inflammasome) and CASP3 (a central mediator of apoptosis) are closely linked to tissue destruction and programmed cell death in chronic inflammatory diseases. Although periodontal disease is fundamentally driven by a dysregulated host inflammatory and immune response to bacterial biofilm, the involvement of STAP-1, STAP-2, and their associated signaling molecules in this process has not previously been investigated. This study will enroll 75 systemically healthy adults, allocated into three groups of 25 participants each based on periodontal status: periodontally healthy, gingivitis, and periodontitis. Diagnosis and group allocation will be based on standard clinical periodontal parameters. From all 75 participants, gingival crevicular fluid (GCF) and unstimulated whole saliva samples will be collected. In addition, gingival tissue biopsies will be obtained from a subset of 60 systemically healthy participants (20 per group), collected during periodontal or extraction procedures that are independently clinically indicated. GCF and saliva samples will be analyzed for total levels of STAP-1, STAP-2, STAT3, STAT5A, NLRP3, and CASP3 using enzyme-linked immunosorbent assay (ELISA). Gingival tissue samples will be analyzed for relative gene expression of the same six molecules using real-time quantitative polymerase chain reaction (RT-qPCR). Clinical periodontal parameters (such as probing depth, clinical attachment level, bleeding on probing, and plaque index) will be recorded for all participants at the time of sampling. Statistical analyses will compare protein and gene expression levels across the three periodontal groups and will assess correlations among STAP-1, STAP-2, STAT3, STAT5A, NLRP3, and CASP3, as well as their relationships with clinical periodontal parameters, within GCF, saliva, and gingival tissue. The study aims to determine whether STAP family proteins and their related inflammatory/apoptotic signaling molecules are differentially expressed according to periodontal disease severity, and whether they may serve as biological indicators involved in the inflammatory and tissue-destructive processes underlying periodontitis.

Inclusion criteria

Inclusion criteria

for the Healthy Control group were: presence of ≥ 20 teeth in the mouth, probing pocket depth (PPD) ≤ 3 mm, the percentage of bleeding sites for the whole mouth < 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Gingivitis group were: presence of ≥ 20 teeth in the mouth, PPD ≤ 3 mm, % of bleeding sites for the whole mouth ≥ 10%, and, on radiographic examination, a distance of ≤ 3 mm between the cemento-enamel junction and the alveolar bone crest in 95% of all teeth. Inclusion criteria for the Stage 3 Periodontitis group were: presence of ≥ 15 teeth in the mouth, more than 30% of teeth affected by periodontal disease, affected teeth exhibiting probing depths of 6 mm or more and clinical attachment loss (CAL) of ≥ 5 mm, vertical bone loss of 3 mm or more, class 2 or 3 furcation involvement, and radiographic evidence of alveolar bone loss extending to the middle third and beyond (33%) in the relevant teeth

Exclusion criteria

Exclusion criteria

for all groups were defined as: presence of any systemic disease, regular use of any medication, smoking, pregnancy or lactation, periodontal treatment within the last 6 months, antibiotic use within the last 6 months, and the presence of prosthetic restorations on the teeth to be sampled.