TREATMENT OF ARTHRITIS WITH ANTISENSE ORIGONUCLEOTIDE FOR TRANSCRIPTION FACTOR NF-κB
| Project/Area Number |
11671446
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | YOKOHAMA CITY UNIVERSITY |
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Principal Investigator |
TAKAGI Toshitaka SCHOOL OF MEDICINE CHRONIC INTRACTABLE DISEASE CENTER INSTRUCTOR, 医学部・付属病院, 講師 (30254171)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | NF-κB / antisense oligonucleotide / mouse collagen-induced arthritis / AP-1 / rheumatoid arthritis / mouse air-pouch / apoptosis / 免疫組織化学 / 軟骨細胞 |
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| Research Abstract |
1. DBA/1J male mice were immunized with bovine type II collagen emulsified with Freund's incomplete adjuvant as a model for rheumatoid arthritis. Five mice were sacrificed at 3,5,7 weeks after the immunization. Knee joints were fixed in 10% neutralized formic acid, decalcified with 0.5% EDTA and embedded in paraffin. Histological changes were evaluated in sections stained with hematoxylin-eosin and immunostaining with rabbit anti-NF-κB p65 polyclonal antibodies (Santa Cruz) using avidin-biotin complex method. NF-κB was positive in synovial lining cells and chondrocytes. The mean rates of NF-κB-positive chondrocye at 3,5 and 7 weeks after the immunization were 43.7%, 68.0% and 79.5%. The rate of mice without treatment was 51.1%.
2. Antisense oligonucleotide for NF-κB designed as 5'-GAA ACAGATCGTCCATGGT or a mismatched sense designed as 5'-GAAACAGATCGTCTATGGT was intraperitonealy injected into the DBA/1J mice 4 weeks after the immunization with type II collagen for 2 weeks every day. Significant inhibition of swelling and redness of pows was not observed. These findings indicated two critical problems as follows. One was a delivery system of the oligonucleotide, and the other was an effect of another transcription factor AP-1. After then we observed AP-1 expression in the lining cells of mouse air-pouch model induced by lipopolysaccharide. Further investigation on these points will be required.
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Report
(3 results)
Research Products
(5 results)
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[Publications] Sakurai S, Takagi T, Okamoto R, Hayashi T, Matsukura Y, Sato MI, Sato M, Kurosaka N, Eguchi J, Ogura K, Koshino T: "Apoptosis of the lining cells and up-regulation of soluble Fas in the exudates of the mouse air pouch induced by lipopolysaccharide. (in Japanese)."J Jpn Orthop Assoc. 73. S1645 (1999)
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