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.
BACKGROUND
The 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).


METHODS
Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1beta 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.


RESULTS
Adiponectin at the concentration of 10 microg/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-1beta. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1beta. 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.


CONCLUSIONS
Adiponectin 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.
Choi
Hyun-Mi
HM
East-West Bone & Joint Research Institute, East-West Neo Medical Center, Kyung Hee University, 149 Sangil-dong, Gangdong-gu, Seoul, 134-727, Republic of Korea. coffee_tree@naver.com
Lee
Yeon-Ah
YA
Lee
Sang-Hoon
SH
Hong
Seung-Jae
SJ
Hahm
Dae-Hyun
DH
Choi
Sang-Yun
SY
Yang
Hyung-In
HI
Yoo
Myung Chul
MC
Kim
Kyoung Soo
KS
D052242:Adiponectin / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000276:immunology; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000276:immunology; D010003:Osteoarthritis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D013585:Synovitis / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism*
D052242:Adiponectin; D042461:Vascular Endothelial Growth Factor A; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1