RESUMEN
Osteoarthritis (OA) is the most common inflammatory joint disease that is mainly characterized by articular cartilage destruction. Forkhead box M1 (FOXM1) is a transcription factor that acts as a critical mediator of inflammatory response. However, the role of FOXM1 in OA has not been investigated. Interleukin (IL)-1ß is a major proinflammatory cytokine, which is associated with cartilage destruction in the pathophysiology of OA. In the present study, we used IL-1ß to stimulate chondrocytes for the establishment of OA in vitro model. We found that FOXM1 was up-regulated in IL-1ß-induced chondrocytes. Knockdown of FOXM1 attenuated IL-1ß-caused decrease in cell viability. Knockdown of FOXM1 suppressed the IL-1ß-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, and IL-6. Besides, several inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2) were also repressed by knockdown of FOXM1. FOXM1 silencing also inhibited the production of matrix metalloproteinases (MMPs) including MMP-3 and MMP-13. Furthermore, we found that knockdown of FOXM1 blocked the IL-1ß-induced NF-κB activation in chondrocytes. These findings indicated that FOXM1 might play an important role in the pathogenesis of OA, suggesting that FOXM1 might be a potential therapeutic target for the treatment of OA.