2015 Fiscal Year Final Research Report
Inhibition of CD44 cleavage suppresses the chondrocyte de-differentiation
| Project/Area Number |
25462366
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Toshihisa 名古屋大学, 医学部附属病院, 講師 (70378032)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| 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 |
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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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| Free Research Field |
整形外科
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