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

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Dec 24

PMID 39716898

Authors

Chenghu Yin

Liangliang Fu

Shuling Guo

Youde Liang

Taizhi Shu

Wenjun Shao

Haibin Xia

Ting Xia

Min Wang

Affiliations

Soon will be listed here.

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-inflammatory cytokine secretion and osteoclast differentiation in macrophages, exacerbating periodontal damage, whereas FAP inhibition reduced macrophage inflammation, collagen degradation, and bone resorption in experimental periodontitis. Therefore, senescent fibroblasts drive the FAP/OLN imbalance through mTOR activation, contributing to periodontitis progression. Consequently, targeting FAP may offer a promising therapeutic strategy for periodontitis.

Citing Articles

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

Yin C, Fu L, Guo S, Liang Y, Shu T, Shao W Adv Sci (Weinh). 2024; 12(7):e2409398.

PMID: 39716898 PMC: 11831441. DOI: 10.1002/advs.202409398.

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