Related Experiment Video
Updated: Jul 10, 2025

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation
Fan Yang1, Peiqi Wang1, Xiaomeng Dong1
1State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Objectives:
Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence.
Materials And Methods:
Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6-methyladenosine (m6A) modification were evaluated. The role of m6A modification in chondrocyte senescence was determined. The therapeutic effects of m6A inhibition in TMJOA were investigated.
Results:
Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6A modification. Moreover, inhibition of m6A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats.
Conclusions:
This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6A inhibition in TMJOA.
More Related Videos
08:42Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants
Published on: January 7, 2019
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Related Concept Videos
Abnormal Proliferation
Replicative Cell Senescence
DNA Damage can Stall the Cell Cycle