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

Background: 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. Objectives: This study aimed to explore the anti-inflammation effect of ezetimibe on mouse chondrocytes. Methods: 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.