| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Despite advances in diagnosis, surgery and epidemiological understandings, any effective treatment to prevent or/and cure from osteoarthritis (OA) have not been discovered. Here we searched the effector molecules potentially playing a central role in the stress transduction that can activate OA changes, and found that small-GTPase Rho and Rac had an opposite effect in the cartilage matrix maintenance. We also found that the activity of TGFb-activated kinase 1(TAK1) could be regulated by Rho/ROCK, and the TAK1 activity induced expression of a tissue degeneration factor Cox-2 in the synovial fibroblast cells. Finally, we examined a defensive role of anti-stress molecule Nrf2 against the stress-mediated OA change and demonstrated that Nrf2 was important to maintain chondrocyte matrix. Our findings provide the basis for new biologic and pharmacological approaches to the prevention and treatment of OA.
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