Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice.
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-beta-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.
Ebina
Kosuke
K
Departments of Orthopaedics and Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Oshima
Kazuya
K
Matsuda
Morihiro
M
Fukuhara
Atsunori
A
Maeda
Kazuhisa
K
Kihara
Shinji
S
Hashimoto
Jun
J
Ochi
Takahiro
T
Banda
Nirmal K
NK
Yoshikawa
Hideki
H
Shimomura
Iichiro
I
D000256:Adenoviridae; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001842:Bone and Bones / Q000276:immunology; D003094:Collagen / Q000276:immunology; D015922:Complement C1q / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology; D013154:Spleen / Q000276:immunology
D052242:Adiponectin; C499919:Adipoq protein, mouse; D000906:Antibodies; D003176:Complement C3; D015922:Complement C1q; D003094:Collagen