Effects of hypoxia/ischemia on catabolic mediators of cartilage in a human chondrocyte, SW1353.

Cells from a human chondrocyte cell line were studied in 1% oxygen and/or a lower glucose concentration (5.5 mM), compared to the routine culture conditions of normoxia and high glucose. HIF-1α, IL-1β, IL-6, IL-8, COX-2, TNFα, LIF, MMP-3, MMP-13, and reactive oxygen species (ROS) were evaluated, respectively. Effects of hypoxia inducing expression of HIF-1α were statistically significant at 72 h (p < 0.05). Increased production of ROS by hypoxia was also observed with passage of time (p < 0.05). The effects of hypoxia on HIF-1α and IL-1β were potentiated by 5.5 mM glucose, especially after 48 h (p < 0.05). IL-8 production was significantly induced in 1% O2, with 5.5 mM glucose (p < 0.01). IL-8 mRNA expression and production in response to IL-1β were potentiated by hypoxia/ischemia (p < 0.05, p < 0.01, respectively). Up-regulation of IL-1β, ROS, and IL-8 by hypoxia/ischemia in human chondrocytes may occur in correlation with HIF-1α. IL-8 response to IL-1β may be potentiated synergically by hypoxia/ischemia, as an effector of hypoxia/ischemia. The results may suggest aggressive biology of the ordinary cartilage hypoxia/ischemia in the context of arthro-degeneration.