Development of new strategy focusing on transcription factor as the therapeutic target for intractable bone and joint disease
| Project/Area Number |
17390417
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
TOMITA Tetsuya Osaka University, Graduate School of Medicine, Assistant Professor (30283766)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Hideki Osaka University, Graduate School of Medicine, Professor (60191558)
SUGAMOTO Kazuomi Osaka University, Graduate School of Medicine, Endowed Chair Professor (40294061)
UEDA Takafumi National Hospital Organization Osaka National Hospital, 臨床研究部, 医師 (00324773)
MYOUI Akira Osaka University, Hospital, Associate Professor (10263261)
TSUMAKI Noriyuki Osaka University, Graduate School of Medicine, Associate Professor (50303938)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | therapy with nucleic acid / arthritis / osteoarthritis / osteosarcoma / lung metastasis / NFkB / E2F / transcription factor / デコイ型核酸医薬 / 破骨細胞 |
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| Research Abstract |
1. In previous research, we could confirm the suppressive effect of NFkB decoy oligonucleotides for arthritis and joint destruction in rat or monkey animal model. We are preparing our plan for clinical application of NFkB decoy oligonucleotides.
2. After the IL-lb stimulation to human primary cultured cartilage, the decrease of expression of aggrecan and type II collagen in cartilage was prevented by adding NFkB decoy oligonucleotides. From this result, the suppressive effect of NFkB decoy oligonucleotides for degeneration and destruction of human cartilage was suggested and it is supposed that NFkB decoy oligonucleotides would have protective effect for human cartilage when injected into the joints of patients suffered from rheumatoid arthritis or osteoarthritis.
3. We confirmed the suppressive effect of NFkB decoy oligonucleotides for arthritis in animal model by injection into the joints. We are now studying whether NFkB decoy oligonucleotides have suppressive effect for arthritis in mouse arthritis model by intravenous administration.
4. We are studying the property of ribbon-type (circular dumbbell-type) decoy oligonucleotides with the intension to increase the stability of oligonucleotides in vivo. In our previous data, ribbon-type decoy oligonucleotides showed higher resistance to degradation when incubated with nuclease or joint fluid. Ribbon-type decoy oligonucleotides are supposed to have higher resistance against nuclease and have higher stability.
5. Intranasal administration of NFkB decoy oligonucleotides decreased the number of lung metastasis and prolonged survival period in murine lung metastatic model implanted with murine osteosarcoma cell line (LM8) which has high metastatic potential to the lung.
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Angiotensin II accelerates osteoporosis by activating osteoclasts2008
Author(s)
Shimizu, H, Nakagami, H, Osako, MK, Hanayama, R, Kunugiza, Y, Kizawa T, Tomita, T, Yoshikawa, H, Ogihara, T, Morishita, R
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Journal Title
FASEB J (Feb 6 Epub ahead of print)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Increase in nuclease resistance and incorporation of NF-kappaB decoy oligodeoxynucleotides by modification of the 3'-terminus2007
Author(s)
Osako, MK, Tomita, N, Nakagami H, Kunugiza, Y, Yoshino, M, Yuyama K, Tomita, T, Yoshikawa, H, Ogihara, T, Morishita, R
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Journal Title
J Gene Med 9(9)
Pages: 812-9
Description
「研究成果報告書概要(欧文)」より
Related Report
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