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

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.

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.

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, TNFA. Notably, STAT3 inhibition decreased the mRNA levels of STAT3-downstream cytokines and the neutrophil chemoattractants CXCL8 and IL36G.

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.