Background The role of adiponectin in the pathogenesis of rheumatoid arthritis was previously studied in relation to the production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLS).
Objectives This study was performed to evaluate the contribution of adiponectin to the production of IL-6, IL-8, VEGF, MMP-1, and MMP-13 in human endothelial cells and osteoblasts in arthritic joints.
Methods Cultured human umbilical vascular endothelial cells (HUVEC) and osteoblasts were stimulated with adiponectin (1 or 10 μg/ml) or IL-1β (0.1 ng/ml) in the presence or absence of hypoxia for 24 hrs. The gene expression patterns of culture supernatants and cells were analyzed by ELISA and PCR, respectively.
Results Adiponectin significantly stimulated the expression of VEGF, MMP-1, and MMP-13 in osteoblasts but not in HUVEC, while it significantly stimulated the expression of IL-6 and IL-8 in both HUVEC and osteoblasts. The increase of VEGF expression by adiponectin was significantly higher than that by IL-1β stimulation. The expression of IL-6 and IL-8 in adiponectin-stimulated HUVEC was about 10-fold higher than that of IL-1β, but about 2-fold higher in osteoblasts. In addition, IL-8 expression levels in HUVEC were about 7-fold higher than that of osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may play an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases observed in gene expression by adiponectin were differentially regulated by hypoxia.
Conclusions Adiponectin plays a more important role in the production of mediators driving synovitis and joint destruction in endothelial cells and osteoblasts than that of IL-1β at physiological concentrations.
Arthritis Res Ther 2009, 11(6):R161
Acknowledgements Basic Science Research Program through the National Research Foundation of Korea (NRF) (grant numbers 2010-0024089 and 2011-0009061)
Disclosure of Interest None Declared