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This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascularendothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts inarthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin(1 or 10 lgml 1) or IL-1b (0.1 ng ml 1) in the presence or absence of hypoxia for 24 h. The protein expression patterns wereexamined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantlystimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantlystimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production inducedby adiponectin was significantly greater than that induced by IL-1b. The production of IL-6 and IL-8 in adiponectin-stimulatedendothelial cells was approximately 10-fold higher than that in IL-1b-stimulated endothelial cells; in osteoblasts, adiponectininducedIL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1b. In addition, IL-8 productionin endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the twocell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have animportant role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced byadiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1b inthe production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiologicalconcentrations.

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