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Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice |
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| Authors: | Kosuke Ebina Kazuya Oshima Atsunori Fukuhara Shinji Kihara Takahiro Ochi Hideki Yoshikawa |
| Affiliation: | a Departments of Orthopaedics and Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan b Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan c Division of Analysis for Pathophysiology, Institute of Clinical Research, National Hospital Organization Kure Medical Center, Kure, Hiroshima 737-0023, Japan d Department of Internal Medicine, National Hospital Organization Kure Medical Center, Kure, Hiroshima 737-0023, Japan e Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan f Division of Rheumatology B115, University of Colorado at Denver and Health Sciences Center, M-20 3104, 1775 North Ursula St., Aurora, CO 80045, USA |
| Abstract: | Adiponectin (APN) is a hormone released by adipose tissue with anti-inflammatory properties. The purpose of this study was to examine the therapeutic effects of systemic delivery of APN in murine arthritis model. Collagen-induced arthritis (CIA) was induced in male DBA1/J mice, and adenoviral vectors encoding human APN (Ad-APN) or beta-galactosidase (Ad-β-gal) as control were injected either before or during arthritis progression. Systemic APN delivery at both time points significantly decreased clinical disease activity scores of CIA. In addition, APN treatment before arthritis progression significantly decreased histological scores of inflammation and cartilage damage, bone erosion, and mRNA levels of pro-inflammatory cytokines in the joints, without altering serum anti-collagen antibodies levels. Immunohistochemical staining showed significant inhibition of complement C1q and C3 deposition in the joints of Ad-APN infected CIA mice. These results provide novel evidence that systemic APN delivery prevents inflammation and joint destruction in murine arthritis model. |
| Keywords: | Adiponectin Collagen-induced arthritis Complement Disease severity Inflammation Mice Rheumatoid arthritis |
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