Wen Li1, Na Wu1, Junming Wang2, Yingnan Wang1, Mengjie Wu1, Hao Wang2. 1. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China. 2. Experimental Teaching Center of Basic Medicine, Fudan University, Shanghai, China.
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.
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.