Laquinimod Mitigated IL-1β-Induced Impairment of the Cartilage Extracellular Matrix in Human ATDC5 Chondrocytes.

Abstract

To date, a safe and reliable treatment of osteoarthritis (OA) has not yet been announced. Inflammatory response and degradation of the articular extracellular matrix (ECM) induced by IL-1β are important pathological characteristics of OA. Laquinimod is a quinoline-3-carboxamide and a novel oral immunomodulatory compound in clinical use. However, whether laquinimod has a beneficial effect in OA is not known. In our research, we found that laquinimod could ameliorate IL-1β-induced generation of ROS and improve mitochondrial function by increasing mitochondrial membrane potential (ΔΨm). Furthermore, treatment with laquinimod suppressed IL-1β-induced production of TNF-α and IL-6. Notably, laquinimod prevented the degradation of type II collagen by inhibiting MMP-3 and MMP-13. Meanwhile, the presence of laquinimod attenuated the reduction in aggrecan by mediating ADAMTS-4 and ADAMTS-5. Mechanistically, laquinimod ameliorated IL-1β-induced inflammation and degeneration of ECM by suppressing the activation of NF-κB. Taken together, our findings reveal that laquinimod possesses a beneficial effect against IL-1β insults in human chondrocytes, implying an important role of laquinimod in OA.