Impact of smoking on gremlin-1, syndecan-4, and IL-1β responses to non-surgical periodontal therapy in stage 3 periodontitis: a comparative study with periodontally healthy controls

Objectives: This study aimed to compare the periodontal status of periodontally healthy individuals with those of smokers and non-smokers with stage 3 periodontitis before and after treatment, as well as to investigate the levels of Gremlin-1, Syndecan-4, and IL-1β in GCF samples. Another objective of the study was to evaluate the relationship between these biomarkers and periodontitis and to assess the effects of smoking on their levels. Materials and methods: A total of 45 volunteers, 15 smokers (Group SP) and 15 non-smokers (Group NP) diagnosed with stage 3 periodontitis between the ages of 18 and 60, and 15 healthy individuals (Group H) were included in the study. Results: All clinical parameters of the SP and NP groups were found to be significantly higher than those of the H group before NSPT (p<0.001), and a significant reduction was observed in all clinical parameters after phase I treatment (p<0.001). Following NSPT, significant improvement was observed in all periodontal parameters in both periodontitis groups (p<0.001). Gremlin-1 levels in the SP and NP groups were statistically significantly lower after treatment compared to pre-treatment levels (p<0.05). While there was no statistically significant difference in IL-1β levels before and after treatment in the SP group (p>0.05), a statistically significant reduction was observed in the NP group after treatment (p<0.05). Similarly, no statistically significant difference was found in Syndecan-4 levels before and after treatment in the SP group (p>0.05), whereas the post-treatment measurements of the NP group were statistically significantly lower (p<0.05). Conclusions: After NSPT, Gremlin-1 levels in GCF decreased in both groups, whereas significant reductions in Syndecan-4 and IL-1β levels were observed only in non-smokers. These findings suggest that the regulatory effect of smoking on biomarkers may negatively influence the periodontal treatment response. Clinical relevance: Smoking is a major risk factor for periodontitis and may impair healing following nonsurgical periodontal therapy. While similar clinical improvements were observed, reductions in IL-1β and Syndecan-4 occurred only in non-smokers, whereas Gremlin-1 decreased in both groups. These findings suggest that smoking may influence molecular healing responses, and biomarker monitoring may support personalized periodontal management.