Vitexin alleviates interleukin-1β-induced inflammatory responses in chondrocytes from osteoarthritis patients: Involvement of HIF-1α pathway

It has been reported that vitexin has anti-inflammatory effects in osteoarthritis (OA) rats. However, the effects of vitexin on interleukins-1 beta (IL-1 beta)-stimulated OA patient-derived chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects of vitexin on IL-1 beta-stimulated human osteoarthritis chondrocytes and to reveal the involvement of hypoxia-inducible factor 1 alpha (HIF-1 alpha) pathway. Enzyme-linked immunosorbent assay, quantitative real-time PCR and Western blotting assays were employed. ELISA results demonstrated that the proinflammatory cytokine levels of interleukins-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) in the serum and synovial fluid and HIF-1 alpha level in the synovial fluid were significantly elevated in OA patients compared to normal healthy subjects. Moreover, the Western blotting results indicated that the protein expression of HIF-1 alpha was significantly higher in the cartilage tissues of OA patients. OA patient-derived chondrocytes were stimulated by IL-1 beta and treated with different concentration of vitexin for 24 hours. Vitexin showed no cytotoxicity and increased the survival of chondrocytes under IL-1 beta stimulation. Vitexin suppressed IL-1 beta-induced production of NO and prostaglandin E2 (PGE(2)) in chondrocytes culture. The treatment of vitexin significantly inhibited IL-1 beta-induced expressions of proinflammatory cytokine levels of IL-6, TNF-alpha, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13. Furthermore, Western blotting results demonstrated that HIF-1 alpha is involved in vitexin's protective effects on IL-1 beta-stimulated injuries in OA patient-derived chondrocytes. Our study demonstrates that vitexin alleviates IL-1 beta-induced inflammatory responses in chondrocytes from osteoarthritis patients, which may be attributed partly to the inhibition of HIF-1 alpha pathway.