Ezetimibe Prevents IL-1β-induced Inflammatory Reaction in Mouse Chondrocytes via Modulating NF-κB and Nrf2/HO-1 Signaling Crosstalk

Osteoarthritis is a type of age-related, chronic, and degenerative joint disease. Ezetimibe, a cholesterol absorption inhibitor, is widely used for the treatment of various diseases. However, the role of ezetimibe in osteoarthritis remains unclear.This study aimed to explore the anti-inflammation effect of ezetimibe on mouse chondrocytes.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.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.On the whole, the present study demonstrates that ezetimibe may be a promising agent for further osteoarthritis therapy.