The molecular mechanism of YAP in regulating osteoclast differentiation in periodontal tissue under mechanical stress
10.3969/j.issn.1671-8348.2025.11.009
- VernacularTitle:应力刺激下YAP调控牙周组织破骨细胞分化的分子机制研究
- Author:
Lili XUE
1
;
Shuai CHEN
;
Bing YAN
Author Information
1. 厦门大学附属第一医院口腔科,厦门 361001
- Keywords:
YAP;
hippo signaling pathway;
occlusal trauma;
periodontitis;
osteoclasts
- From:
Chongqing Medicine
2025;54(11):2528-2537
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of Yes-associated protein(YAP)in bone resorption exac-erbated by occlusal trauma during periodontitis and its molecular mechanisms,and to evaluate the interven-tional effect of YAP inhibition on alveolar bone destruction.Methods Osteoclasts were stimulated by in vitro mechanical loading combined with lipopolysaccharide(LPS)to simulate the in vitro synergistic effect of occlu-sal stress and inflammation.A murine periodontitis model with occlusal trauma was established.Flow cytome-try,Western blot,qPCR,and immunofluorescence staining were employed to analyze YAP dephosphorylation and nuclear translocation in cellular and animal models,and to investigate YAP's regulatory effect on the c-Jun N-terminal kinase(JNK)/receptor activator of nuclear factor kappa-B ligand(RANKL)pathway.The YAP inhibitor XAV939 was administered to evaluate its impact on osteoclast activation and bone resorption through pathway intervention.Results In vitro,combined mechanical stress and LPS stimulation significantly reduced YAP phosphorylation in osteoclasts,promoted YAP nuclear translocation,and activated the JNK-RANKL pathway.In vivo,the periodontitis with occlusal trauma group exhibited markedly elevated expres-sion of YAP,JNK,and RANKL compared to the periodontitis-alone group(P<0.001).XAV939 intervention reversed YAP nuclear translocation,suppressed JNK phosphorylation and RANKL expression(P<0.01),and reduced osteoclast numbers.Conclusion YAP acts as a central hub integrating mechanical and inflammatory signals,exacerbating osteoclast differentiation and bone resorption via activation of the JNK-RANKL axis.Targeted inhibition of YAP effectively blocks this pathological cascade,offering a new approach for the precise treatment of periodontitis complicated by occlusal trauma.
