Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In this study, we not only confirmed the findings in our previous study that ICA promoted chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, this study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

中文翻译：

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Icariin通过下调软骨细胞中的NF-κB/HIF-2α信号通路来抑制炎症。

关节软骨损伤或缺损是一种常见疾病，其主要特征是由于软骨细胞发炎导致软骨退化。到目前为止，还没有有效的药物和方法来保护关节软骨免于降解。Icariin（ICA）是从Epimedii Folium中提取的一种典型的类黄酮化合物，具有抗炎和保护骨骼的作用。我们以前的研究表明，ICA上调了软骨细胞中HIF-1α的表达和糖酵解，并维持了软骨细胞的表型。作为HIFs家族的另一个成员，HIF-2α始终在炎症中起关键作用。到目前为止，ICA对HIF-2α的作用尚不清楚。在这项研究中，我们不仅证实了先前研究的发现，即ICA促进了软骨细胞活力和细胞外基质（ECM）的合成，而且还具有ICA的抗炎作用。在骨缺损小鼠中，ICA抑制NF-κB和HIF-2α的表达。在TNF-α处理的ADTC5软骨细胞中，ICA中和了IKK的激活（IKK磷酸化），IkB和NF-κB的磷酸化以及HIF-2α的表达。此外，ICA抑制了NF-κB/HIF-2α信号通路的两个关键靶点NF-κB的核转移以及MMP9和ADAMTS5的表达。两者合计，这项研究表明ICA可能通过抑制NF-κB/HIF-2α信号通路抑制炎症损伤，从而增加软骨细胞的活力。ICA是一种治疗关节软骨损伤的有效候选药物。IkB和NF-κB的磷酸化和HIF-2α的表达。此外，ICA抑制了NF-κB/HIF-2α信号通路的两个关键靶点NF-κB的核转移以及MMP9和ADAMTS5的表达。两者合计，这项研究表明ICA可能通过抑制NF-κB/HIF-2α信号通路抑制炎症损伤，从而增加软骨细胞的活力。ICA是一种治疗关节软骨损伤的有效候选药物。IkB和NF-κB的磷酸化和HIF-2α的表达。此外，ICA抑制了NF-κB/HIF-2α信号通路的两个关键靶点NF-κB的核转移以及MMP9和ADAMTS5的表达。两者合计，这项研究表明ICA可能通过抑制NF-κB/HIF-2α信号通路抑制炎症损伤，从而增加软骨细胞的活力。ICA是一种治疗关节软骨损伤的有效候选药物。