TY - JOUR
T1 - Thrombospondin 1 as an effective gene therapeutic strategy in collagen-induced arthritis
AU - Jou, I. Ming
AU - Shiau, Ai Li
AU - Chen, Shih Yao
AU - Wang, Chrong Reen
AU - Shieh, Dar Bin
AU - Tsai, Ching Shan
AU - Wu, Chao Liang
PY - 2005/1
Y1 - 2005/1
N2 - Objective. Because thrombospondin 1 (TSP-1) inhibits angiogenesis and activates latent transforming growth factor β (TGFβ), a potent immunosuppressive and antiinflammatory cytokine, we investigated the prophylactic and therapeutic effects of TSP-1 gene transfer in the collagen-induced arthritis (CIA) model in rats. Methods. Adenoviral vectors encoding mouse TSP-1 (AdTSP-1) or β-galactosidase (AdLacZ) as the control were administered by intraarticular injection into CIA rats. The treated ankles were assessed clinically, radiographically, and histologically. Furthermore, expression levels of TSP-1, TGFβ, vascular endothelial growth factor (VEGF), and interieukin-1β (IL-1β) were examined in the synovial tissue. Results. Intraarticular administration of AdTSP-1 reduced the severity of CIA as revealed by examination of the clinical, radiographic, and histologic aspects. Rats treated with AdTSP-1, as compared with AdLacZ-treated controls, were found to have fewer blood vessels (mean ± SEM 21.0 ± 0.6 versus 45.3 ± 2.3/mm2; P < 0.001) and lower production of VEGF (17 ± 4 versus 45 ± 10 pg/mg of total protein; P < 0.05) and IL-1β (374 ± 41 versus 526 ± 39 pg/mg of total protein; P < 0.05), as well as higher levels of TSP-1 and TGFβ in the synovial tissue. Conclusion. Direct intraarticular administration of adenoviral vectors encoding TSP-1 significantly ameliorated the clinical course of CIA, accompanied by reduction of synovial hypertrophy and fewer blood vessels. These results suggest that TSP-1 gene therapy may have therapeutic potential for the management of rheumatoid arthritis.
AB - Objective. Because thrombospondin 1 (TSP-1) inhibits angiogenesis and activates latent transforming growth factor β (TGFβ), a potent immunosuppressive and antiinflammatory cytokine, we investigated the prophylactic and therapeutic effects of TSP-1 gene transfer in the collagen-induced arthritis (CIA) model in rats. Methods. Adenoviral vectors encoding mouse TSP-1 (AdTSP-1) or β-galactosidase (AdLacZ) as the control were administered by intraarticular injection into CIA rats. The treated ankles were assessed clinically, radiographically, and histologically. Furthermore, expression levels of TSP-1, TGFβ, vascular endothelial growth factor (VEGF), and interieukin-1β (IL-1β) were examined in the synovial tissue. Results. Intraarticular administration of AdTSP-1 reduced the severity of CIA as revealed by examination of the clinical, radiographic, and histologic aspects. Rats treated with AdTSP-1, as compared with AdLacZ-treated controls, were found to have fewer blood vessels (mean ± SEM 21.0 ± 0.6 versus 45.3 ± 2.3/mm2; P < 0.001) and lower production of VEGF (17 ± 4 versus 45 ± 10 pg/mg of total protein; P < 0.05) and IL-1β (374 ± 41 versus 526 ± 39 pg/mg of total protein; P < 0.05), as well as higher levels of TSP-1 and TGFβ in the synovial tissue. Conclusion. Direct intraarticular administration of adenoviral vectors encoding TSP-1 significantly ameliorated the clinical course of CIA, accompanied by reduction of synovial hypertrophy and fewer blood vessels. These results suggest that TSP-1 gene therapy may have therapeutic potential for the management of rheumatoid arthritis.
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U2 - 10.1002/art.20746
DO - 10.1002/art.20746
M3 - Article
C2 - 15641039
AN - SCOPUS:12344331258
SN - 0004-3591
VL - 52
SP - 339
EP - 344
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 1
ER -