passages: PMC-3003518-sec-05__text
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passages: Introduction
  Adipose tissue, once viewed as simply a storage and release depot for lipids, is now considered an endocrine tissue [1,2] that secretes various substances (adipokines), including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, leptin, adiponectin, resistin, visfatin, and omenetin [3,4]. Among these adipokines, much attention has been paid to adiponectin's relationship with insulin sensitivity and glucose and lipid metabolism in the past 10 years. In addition, adiponectin is known to exhibit potent anti-inflammatory [5], atheroprotective [6], and antidiabetic [7] effects.
  Recent findings suggest that adiponectin may be involved in the pathogenesis of rheumatoid arthritis (RA). Levels of adiponectin in synovial fluid and sera were elevated in patients with RA [8,9]. Adiponectin also induces the production of proinflammatory cytokines, IL-6, matrix metalloproteinase (MMP)-1, and IL-8 from RA synovial fibroblasts in vitro [10,11]. Thus, it was suggested that adiponectin can also exert significant proinflammatory and matrix-degrading effects. However, the role of adiponectin in the pathogenesis of RA is still controversial because of conflicting reports about its function [10,12-15]. In particular, adiponectin seems to play an anti-inflammatory role because it significantly inhibited IL-1beta-stimulated synovial cell proliferation in collagen-induced arthritic mice, despite increased IL-6 expression [16]. In contrast, high-grade inflammation in RA patients was negatively correlated with circulating adiponectin concentrations [17]. Rather, it was suggested that circulating adiponectin may be involved in cardiovascular disease in RA patients. Although this contradiction was partly explained by the induction of tolerance to inflammatory stimuli by adiponectin [18], the pro- or anti-inflammatory effects of adiponectin on the pathogenesis of RA remain unknown.
  With regard to adiponectin's proinflammatory effects, we wondered whether adiponectin might stimulate the production of vascular endothelial growth factor (VEGF) and MMPs as well as proinflammatory mediators like IL-1beta and TNF-alpha do. In this study, we investigated the stimulatory effect of adiponectin on the production of IL-6, IL-8, prostaglandin E2 (PGE2), VEGF, and MMPs. In addition, the correlation between adiponectin and VEGF or MMPs was investigated by measuring the levels of these three proteins in the joint fluid of patients with RA or osteoarthritis (OA).
  