Peri‐Implantitis‐Associated Bacteria Activate the STAT3 Pathway in Oral Epithelial Cells

ABSTRACT Aim To assess STAT3 activation in peri‐implantitis tissues and to evaluate the STAT3‐associated response of oral epithelial cells (OECs) to peri‐implantitis‐associated bacteria. Methods In this cross‐sectional study, gingival tissue biopsies were obtained from subjects with gingival health, periodontitis and peri‐implantitis. pSTAT3/STAT3 and STAT3 pathway‐dependent mRNA levels were analysed, and pSTAT3‐positive cells were assessed by immunofluorescence. Additionally, OECs were stimulated with S. sanguinis , P. gingivalis and F. nucleatum , as well as with bacterial communities from the three conditions. STAT3 pathway–associated mRNA levels and the pSTAT3/STAT3 ratio were evaluated. Finally, the effect of pSTAT3 inhibition was analysed. Results Increased STAT3 pathway activation was observed in peri‐implantitis tissues, characterised by a higher pSTAT3/STAT3 ratio and elevated IL6 and SOCS3 mRNA levels. Compared with healthy gingival tissues and periodontitis, peri‐implantitis tissues exhibit a higher proportion of pSTAT3‐positive epithelial cells. P. gingivalis and F. nucleatum increased the mRNA of the STAT3‐associated IL6 , IL23A , SOCS3 , chemoattractant‐associated CXCL8 , IL36G and inflammation‐associated IL1B , TNF A. Notably, STAT3 inhibition decreased the mRNA levels of STAT3‐downstream cytokines and the neutrophil chemoattractants CXCL8 and IL36G . Conclusion The STAT3 pathway is activated in peri‐implantitis and in OECs and is elicited by peri‐implantitis‐associated bacteria, contributing to a pro‐chemotactic epithelial environment, positioning this pathway as a key area of interest for future research into the molecular mechanisms underlying both conditions.