Search

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. [ABSTRACT FROM AUTHOR]