Role of HIF-2α/NF-κB pathway in mechanical stress-induced temporomandibular joint osteoarthritis.
Oral Dis
; 28(8): 2239-2247, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-34342085
ABSTRACT
OBJECTIVES:
Many activities overload temporomandibular joint (TMJ) and cause mandibular condylar cartilage (MCC) degradation by inducing the expression of hypoxia-inducible factor-2α (HIF-2α). Although NF-κB signaling pathway has been reported to induce HIF-2α expression, the underlying mechanisms need to be verified. The aim was to investigate the effects of NF-κB/HIF-2α on MCC degradation induced by mechanical stress and the regulatory mechanism of NF-κB in the HIF-2α pathway.METHODS:
Chondrocytes were subjected to cyclic compressive forces in a hypoxic environment. Western blotting was used to test the effects of stress on the expression of NF-κB and HIF-2α. HIF-2α siRNA and shRNA were constructed and transfected into MCC cells in vitro and in vivo to inhibit HIF-2α expression. To test the regulatory effect of the NF-κB pathway on HIF-2α, siRNA p65 was transfected into MCC.RESULTS:
The results showed that mechanical stress could cause cartilage degradation and significantly increased the expression of NF-κB, HIF-2α, and downstream degradation factors (MMP13 and ADAMTs-4). Blockade of HIF-2α decreased cartilage degradation and related degradation factors. Suppression of p65 significantly decreased the expression of HIF-2α.CONCLUSIONS:
Our results indicated that the upstream NF-κB pathway exerted a regulatory effect on HIF-2α in the degradation of MCC induced by stress.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
NF-kappa B
Limite:
Humans
Idioma:
En
Revista:
Oral Dis
Assunto da revista:
ODONTOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China