Icariin increases chondrocyte vitality by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis.

Articular cartilage is a unique avascular tissue in which chondrocytes are embedded in extracellular matrix (ECM). The decreased ECM resulting from the loss of articular chondrocyte viability leads to degenerative diseases such as osteoarthritis (OA). This study aims to investigate the effect of icariin (ICA) on ECM synthesis and chondrocyte viability. Micromass culture, alcian blue, and Safran O (SO)/fast green staining were used to investigate chondrocyte viability and ECM synthesis in chondrocytes treated with ICA. The expression of hypoxia-inducible factor-1α (HIF-1α), SOX9, and anaerobic glycolysis enzymes were detected by western blot and reverse transcription-quantitative polymerase chain reaction. ICA, an active flavonoid component of Herba epimedii, was demonstrated to increase chondrocyte viability and ECM synthesis. HIF-1α is a key mediator of chondrocyte response to fluctuations in oxygen availability during cartilage development or damage, and its expression was unregulated by ICA treatment. Meanwhile, ICA treatment increased SOX9 expression, which is a key regulator of ECM synthesis. Furthermore, ICA treatment increased the expression of glucose transporter 1 (GLUT1), glucose-6-phosphate dehydrogenase (G6PD), phosphoglycerate kinase 1 (PGK1), and pyruvate dehydrogenase kinase 1 (PDK1), which contribute to glucose transfer and anaerobic glycolysis. The present study revealed that ICA treatment facilitates chondrocyte vitality by promoting HIF-1α expression and anaerobic glycolysis. Therefore, ICA could be a novel clinical treatment for OA.