Adiponectin mitigates the severity of arthritis in mice with collagen-induced arthritis.
OBJECTIVE
Adiponectin (AD) is considered an inflammation modulator. In this study, we investigated the effect of AD on rheumatoid arthritis (RA) using a collagen-induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF).


METHODS
Fifteen DBA/1 mice were divided into three groups. All mice, except the control group, were injected with type II collagen. AD was intra-articularly injected in the left hind legs after arthritis development (the AD-treated group). The severity of the arthritis was measured using an arthritis score and paw thickness. A histopathological assessment of joint sections was performed by haematoxylin/eosin (H&E) staining. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-3 expression was evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was obtained from four RA patients during total joint replacement. RASF cultures were established from this tissue. RASF were pretreated with AD and stimulated by TNFalpha or IL-1beta. TNFalpha, IL-1beta, IL-6, and MMP-3 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). RASF proliferation was evaluated using the MTT assay.


RESULTS
AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNFalpha, IL-1beta, and MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues increased. Moreover, AD reduced TNFalpha, IL-1beta, and MMP-3 expression in stimulated RASF and increased IL-6 expression in IL-1beta-stimulated RASF. AD significantly inhibited IL-1beta-induced RASF proliferation, despite increased IL-6 expression.


CONCLUSIONS
These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.
Lee
S-W
SW
Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul, South Korea.
Kim
J-H
JH
Park
M-C
MC
Park
Y-B
YB
Lee
S-K
SK
D052242:Adiponectin / Q000502:physiology*; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007719:Knee Joint / Q000503:physiopathology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D013583:Synovial Membrane / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019278:Matrix Metalloproteinase 3