Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.
Oral Dis
; 2023 Nov 20.
Article
en En
| MEDLINE
| ID: mdl-37983852
ABSTRACT
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 ANDMETHODS:
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 (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A 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 m6 A modification. Moreover, inhibition of m6 A 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 m6 A inhibition in TMJOA.
Texto completo:
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Base de datos:
MEDLINE
Idioma:
En
Revista:
Oral Dis
Asunto de la revista:
ODONTOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China