Salivary growth differentiation factor-15 is elevated with reduced gingival crevicular fluid SMAD5 and SMAD6 levels in periodontitis: a cross-sectional study

Abstract This study evaluated Growth differentiation factor-15 (GDF-15), SMAD2, SMAD5, SMAD6 and Interleukin-6 (IL-6) levels in gingival crevicular fluid (GCF) and saliva in periodontitis and periodontal health, and assessed relationships with clinical periodontal parameters. Forty-four systemically healthy individuals were enrolled, including 22 patients with Stage III/Grade B periodontitis and 22 periodontally healthy controls. Plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. GDF-15, SMAD2, SMAD5, SMAD6 and IL-6 levels were measured using ELISA. GCF SMAD5 and SMAD6 were significantly lower in periodontitis (p < 0.0001 and p = 0.0057, respectively), whereas salivary GDF-15 and both GCF and salivary IL-6 were higher than controls (p = 0.0177, p = 0.0008, and p = 0.0017, respectively). GCF GDF-15 did not differ significantly between groups (p = 0.0814). GCF SMAD6 correlated negatively with GCF IL-6 (r = − 0.461, p = 0.0016) and PPD, PI, BOP, and CAL (r = − 0.448 to − 0.353, p < 0.05). GCF IL-6 correlated positively with PPD, PI, and CAL (r = 0.309–0.353, p < 0.05). ROC discriminatory performance was highest for GCF IL-6 (AUC = 0.786, p < 0.001) and GCF SMAD5 (AUC = 0.770, p < 0.001). Stage III/Grade B periodontitis was associated with increased salivary GDF-15, increased IL-6 levels in both GCF and saliva, and decreased GCF SMAD5 and SMAD6 levels, suggesting an altered inflammatory and SMAD-related oral-fluid biomarker profile. GCF IL-6 and GCF SMAD5 may represent candidate adjunctive biomarkers for further evaluation in larger independent cohorts alongside conventional clinical periodontal parameters. Clinical trial registration: NCT07201142.