a new disease-modifying osteoarthritis drug (DMOAD) candidate using a cell based screening system
Project/Area Number |
24659665
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Orthopaedic surgery
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Research Institution | The University of Tokyo |
Principal Investigator |
YANO Fumiko 東京大学, 医学部附属病院, 助教 (80529040)
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Co-Investigator(Kenkyū-buntansha) |
MORIZAKI Yutaka 東京大学, 医学部附属病院, 助教 (30508099)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | 変形性膝関節症 / 軟骨再生 / 低分子化合物 |
Outline of Final Research Achievements |
To identify a new disease-modifying osteoarthritis drug (DMOAD) candidate, we screened 2500 synthetic small compounds for chondrogenic agents via four steps using the Col2GFP-ATDC5 system and identified a small thienoindazole derivative compound, TD-198946, as a novel DMOAD candidate. We tested its efficacy as a DMOAD via intra-articular injections directly into the joint space in a mouse model of OA both at the onset (prevention model) and 4 weeks after (repair model). We further investigated the mechanism of the drug action and its molecular target using in vitro (DNA microarray analysis and Proteomic analysis) and in vivo assays. TD-198946 strongly induced chondrogenic differentiation without promoting hypertrophy and successfully prevented and repaired degeneration of the mouse articular cartilage. TD-198946 exerted its effect through the regulation of Runx1 expression.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation2013
Author(s)
Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
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Journal Title
PLoS One
Volume: 16;8(9)
Issue: 9
Pages: e74137-e74137
DOI
Related Report
Peer Reviewed
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[Journal Article] Tenomodulin expression in the periodontal ligament enhances cellular adhesion2013
Author(s)
Y. Komiyama, S. Ohba, N. Shimohata, K. Nakajima, H. Hojo, F. Yano, T. Takato, D. Docheva, C. Shukunami, Y. Hiraki, and UI. Chung.
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Journal Title
PLoS One
Volume: 8
Issue: 4
Pages: e60203-e60203
DOI
Related Report
Peer Reviewed
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[Journal Article] β-catenin regulates PTH/PTHrP receptor signals and chondrocyte hypertrophy through binding to its intracellular C-terminal region2013
Author(s)
Yano, F., Saito, T., Ogata, N., Yamazawa, T., Iino, M., Chung, U.I. and Kawaguchi, H
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Journal Title
Arthritis Rheum
Volume: 65
Issue: 2
Pages: 429-435
DOI
Related Report
Peer Reviewed
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[Journal Article] Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein(BMP) signaling.2013
Author(s)
Ogasawara T, Ohba S, Yano F, Kawaguchi H, Chung UI, Saito T, Yonehara Y, Nakatsuka T, Mori Y, Takato T, and Hoshi K
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Journal Title
J Cell Physiol
Volume: (in press)
Issue: 1
Pages: 163-71
DOI
Related Report
Peer Reviewed
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[Journal Article] Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage2012
Author(s)
Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A, Ohto T, Kita Y, Nakamura M, Suzuki S, Mochizuki M, Shimizu T, Chung UI, Sasaki N
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Journal Title
J Transl Med
Volume: 10
Issue: 1
Pages: 80-80
DOI
Related Report
Peer Reviewed
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[Presentation] A novel disease-modifying osteoarthritis drug candidate targeting Runx1.2013
Author(s)
Fumiko Yano, Yoko Hosaka, Atsushi Fukai, Taku Saito, Hironori Hojo, Shinsuke Ohba, Hiroshi Kawaguchi, Tsuyoshi Takato, Ung-il Chung
Organizer
Frontiers 2013 EPFL Symposium.
Place of Presentation
Swiss Federal Institute of Technology in Lausanne, Lausanne, Switzerland
Related Report
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