| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
We mainly demonstrated that the excess mechanical stress loading can induce the CD44 fragmentation via the activation of TRPV4, a primary mechano-receptor, and the increased ADAM10 expression. CD44 fragmentation results in decreased ‘functional’ hyaluronan receptors and increased CD44 intracellular domain, leading to the diminished extracellular matrix in a chondrocyte. We also demonstrated that we successfully suppress the CD44 fragmentation using a TRPV4 antagonist or ADAM10 inhibitors under the mechanical stress loading condition. We will be able to start the in vivo study using animal osteoarthritis models as a next step.
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