Inhibition of CD44 cleavage suppresses the chondrocyte de-differentiation
Project/Area Number |
25462366
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Nagoya University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
KOJIMA Toshihisa 名古屋大学, 医学部附属病院, 講師 (70378032)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
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)
|
Keywords | 変形性関節症 / ヒアルロン酸 / CD44 / 断片化 / メカニカルストレス / CD44断片化 / ADAM10 / スタチン / 関節軟骨変性 |
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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Report
(3 results)
Research Products
(13 results)