Curcumin exerts a protective effect on murine knee chondrocytes treated with IL-1β through blocking the NF-κB/HIF-2α signaling pathway

BACKGROUND: Osteoarthritis (OA) is characterized by erosion and degradation of articular cartilage. This study assessed the effects of curcumin on mouse knee cartilage chondrocytes. METHODS: Chondrocytes were treated for 24 hours with interleukin IL-1β (10 ng/mL) alone, or the combination of curcumin (10, 20, and 50 µM) and IL-1β. The proliferation, viability, and cytotoxicity of the chondrocytes were evaluated by the MTS assay. Expression of SOX9, AGG, Col2α, MMP9, ADAMTS5, COX2, iNOS, pIκB-α, pNF-κB, and hypoxia-inducible factor-2α (HIF-2α) were detected by western blotting or quantitative polymerase chain reaction (q-PCR). Nuclear translocation of NF-κB and HIF-2α were investigated by immunofluorescence and immunohistochemistry. In in vivo experiments, mice were subjected to destabilization of the medial meniscus (DMM) and given curcumin orally for 6 weeks. Cartilage integrity was evaluated by OARSI (Osteoarthritic Research Society International) scores. RESULTS: Curcumin significantly inhibited the IL-1β-induced reduction of cell viability, degradation of ECM, and the expression of SOX9, Col2α, and AGG (P<0.01). Western blotting, immunofluorescence and immunohistochemistry experiments demonstrated that curcumin dramatically inhibited the activation of NF-κB/HIF-2α in chondrocytes treated with IL-1β (P<0.01). The articular scores were significantly lower in the DMM-induced OA mice compared to OA mice treated with curcumin (P<0.01). CONCLUSIONS: Curcumin may have the potential to inhibit OA development, partly through suppressing the activation of the NF-κB/HIF-2α pathway.