Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fibroblast-like synoviocytes more than proinflammatory mediators

Abstract

IntroductionThe role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).MethodsSynovial cells from RA patients were treated with adiponectin or interleukin (IL)-1β for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E2 (PGE2), VEGF, and MMPs by enzyme-linked immunosorbent assay. The levels of adiponectin, VEGF, MMP-1, and MMP-13 in the joint fluids from 30 RA or osteoarthritis (OA) patients were also measured.ResultsAdiponectin at the concentration of 10 μg/mL stimulated the production of IL-6, IL-8, and PGE2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1β. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1β. In addition, the level of adiponectin and MMP-1 in the joint fluid of RA patients was significantly higher than in OA patients. Adiponectin was positively correlated with VEGF in RA patients but not in OA patients, while the level of MMPs in joint fluid was not correlated with adiponectin in either RA or OA patients.ConclusionsAdiponectin may play a significant role in the pathogenesis of RA by stimulating the production of VEGF and MMPs in FLSs, leading to joint inflammation and destruction, respectively.

Cartilage oligomeric matrix protein and matrix metalloproteinase-3 expression in the serum and joint fluid of a reversible osteoarthritis rabbit model

“…It can regulate the enzymatic activity of other MMPs such as MMP-1 and MMP-9, and promote collagen degradation, extracellular matrix destruction, and joint swelling, to reduce resistance to external force. With the help of the stress load, it can cause cartilage destruction (Choi et al, 2009;Tong et al, 2011). Our study showed that MMP-3 levels were significantly elevated in articular cartilage lesions.…”

Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases?

“…Of note, adiponectin serum levels in patients with RA but not in patients with OA correlate with VEGF levels (33). Interestingly, other key factors driving arthritis such as TNF␣ and IL-1␤ were not induced by adiponectin in RASFs (26).…”

“…When stimulated with adiponectin, synovial fibroblasts (SFs), the central cells of cartilage destruction in RA, secrete increased amounts of proinflammatory cytokines such as IL-6, a variety of chemokines including IL-8 and growth-related oncogene ␣, proangiogenic factors such as vascular endothelial growth factor (VEGF), and matrix-degrading proteins including matrix metalloproteinase 1 (MMP-1) and MMP-13 (26,(33)(34)(35)(36). Of note, adiponectin serum levels in patients with RA but not in patients with OA correlate with VEGF levels (33).…”

Dose-dependent effects of adiponectin on ADAMTS-9 gene expression in human chondrocytes

“…It was demonstrated that adiponectin increased infl ammatory interleukin-6 (IL-6) (26) and interleukin-8 (27) in synovial fi broblast cells. Besides, the upregulation of matrix metalloproteinase (MMP) -1 and -13 genes expression level in fi broblast-like cell was demonstrated by Choi et al (28). The relationship between adiponectin and other MMPs (MMP-2 and MMP-3) was also showed by other researchers (29,30).…”