Knockdown of FOXM1 attenuates inflammatory response in human osteoarthritis chondrocytes
International Immunopharmacology(2019)
摘要
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)-1β is a major proinflammatory cytokine, which is associated with cartilage destruction in the pathophysiology of OA. In the present study, we used IL-1β to stimulate chondrocytes for the establishment of OA in vitro model. We found that FOXM1 was up-regulated in IL-1β-induced chondrocytes. Knockdown of FOXM1 attenuated IL-1β-caused decrease in cell viability. Knockdown of FOXM1 suppressed the IL-1β-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-1β-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.
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关键词
OA,FOXM1,IL,NO,PGE2,iNOS,COX-2,FABP4
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