Senescent Fibroblasts Drive FAP/OLN Imbalance Through mTOR Signaling to Exacerbate Inflammation and Bone Resorption in Periodontitis.

ABSTRACT: Fibroblast activation protein (FAP), predominantly expressed in activated fibroblasts, plays a key role in inflammatory bone diseases, but its role in periodontitis remains unclear. Accordingly, this study identified a positive association between FAP levels and periodontitis susceptibility using Mendelian randomization analysis. Human and mouse periodontitis tissues show elevated FAP and reduced osteolectin (OLN), an endogenous FAP inhibitor, indicating a FAP/OLN imbalance. Single-cell RNA sequencing revealed gingival fibroblasts (GFs) as the primary FAP and OLN source, with periodontitis-associated GFs showing increased reactive oxygen species, cellular senescence, and mTOR pathway activation. Rapamycin treatment restored the FAP/OLN balance in GFs. Recombinant FAP increased pro-inflamma

SUBMITTER: Yin C 

PROVIDER: S-EPMC11831441 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature