| 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)
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| 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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