ENDOCAN MODULATES VEGF SIGNALING IN IL-1ß ACTIVATED CHONDROCYTES

PURPOSE: to investigate endocan expression and the underlying molecular mechanisms in human chondrocytes stimulated with IL-1. METHODS: chondrocytes were cultured and stimulated with IL-1. A separate set of chondrocytes were incubated with a specific NF-kB inhibitor or a small interfering RNA against endocan mRNA before IL-1 addition. Endocan, VEGFR-2 and ERK expression were evaluated. RESULTS: IL-1 was able to increase significantly endocan expression as well as NF-kB activity. On the contrary, in chondrocytes treated with NF-kB inhibitor , the effects of IL-1 on endocan expression was significantly reduced. In endocan knockdown cells we found a decrease in VEGF signaling pathways. DISCUSSION: endocan was found highly expressed in arthritic synovial tissues from patients with rheumatoid arthritis or osteoarthritis. In these settings, endocan could be involved in the mechanisms that stimulate cell invasion, cell migration, and angiogenesis in the pannus of arthritic joints. Our data, consistent with previous results in other cell type and tissues, demonstrate that endocan released during inflammatory response in chondrocytes modulates VEGF signaling that is crucial in angiogenesis. CONCLUSION: these findings indicate that endocan is a modulator of VEGF signaling in activated chondrocytes, suggesting a possible role in inflammation and angiogenesis observed in arthritis; therefore, the inhibition of endocan release may prevent cartilage joint damage.