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Ezetimibe prevents IL-1β-induced inflammatory reaction in mouse chondrocytes via modulating NF-κB and Nrf2/HO-1 signaling crosstalk.

Qiuyan Weng,Tongzhou Hu,Xiaohan Shen,Jinming Han,Yong Zhang,Jianning Luo

Published 2022 in Current Pharmaceutical Biotechnology

ABSTRACT

BACKGROUND Osteoarthritis, a type of age-related, chronic, degenerative joint disease. Ezetimibe, a cholesterol absorption inhibitor, is widely used for the treatment of various diseases. The role of ezetimibe in osteoarthritis remains unclear. OBJECTIVE This study aimed to explored the anti-inflammation effect of ezetimibe on mouse chondrocytes. METHOD In the present study, ELISA, qPCR and western blot analysis were performed to evaluate the anti-inflammatory effects of ezetimibe. In addition, enzymes that are highly associated with the anabolism and catabolism of the extracellular matrix of the articular cartilage were also evaluated. RESULTS Treatment with ezetimibe attenuated the IL-1β-induced degradation of the extracellular matrix, including aggrecan and collagen II. Ezetimibe also attenuated the IL-1β-induced expression levels of MMP3, MMP13 and ADAMTS5, thus exerting protective effects against IL-1β-induced extracellular matrix degradation. The complex mechanism of the anti-inflammatory reaction contributed to the activation of the Nrf2/HO-1 pathway and the suppression of the NF-κB pathway. CONCLUSION On the whole, the present study demonstrates that ezetimibe may be a promising agent for further osteoarthritis therapy.

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