FTO-associated Osteoclastogenesis Promotes Alveolar Bone Resorption in Apical Periodontitis Male Rat Via the HK1/USP14/RANK Pathway

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Feb 11

PMID 39934129

Authors

Yajie Qian

Jing Wu

Weidong Yang

Ruining Lyu

Qiao You

Jingjing Li

Qin He

Yuan Zhuang

Wenmei Wang

Yong Wang

Yanan Zhu

Zhiwei Wu

Deyan Chen

Affiliations

Soon will be listed here.

Abstract

Alveolar bone resorption (ABR) is a key pathological manifestation in the development of apical periodontitis (AP) and contributes to the AP-associated tooth loss among AP patients in the clinic. However, the underlying mechanism of ABR development is largely unknown. Here we show, the total levels of N6-methyladenosine (mA) were reduced in AP male rat alveolar bone tissues and BMDM-derived osteoclasts (OC), which was associated with the up-regulation of obesity-associated protein (FTO). Subsequently FTO-mediated hexokinase (HK1) demethylation modification enhancing glycolytic pathway that stabilizes receptor activator of NF-κB (RANK) protein via the deubiquitination activity of ubiquitin-specific protease 14 (USP14), which further promotes osteoclastogenesis to participate in the AP-related ABR development. Finally, Dac51 (an FTO inhibitor) and 2-DG (an HK1 inhibitor) both exhibit the inhibitory activity of osteoclastogenesis. Our current study reveals a molecular mechanism on osteoclastogenesis-related ABR and provides a therapeutic target of AP via modulating the FTO/HK1/USP14/RANK axis.

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