R-spondin2 activation of Wnt/b-catenin signaling in chondrocytes and prevention of osteoarthritis
Project/Area Number |
18K09062
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Nagoya University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
関 泰輔 名古屋大学, 医学部附属病院, 病院講師 (20528822)
宮本 健太郎 名古屋大学, 医学部附属病院, 医員 (50789899)
樋口 善俊 名古屋大学, 医学部附属病院, 医員 (80792738)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | Wntシグナル / 変形性関節症 / 軟骨代謝 / Rspo2 / 軟骨 / ドラッグリポジショニング / 軟骨細胞 |
Outline of Final Research Achievements |
In this study, we hypothesized that abnormalities in Rspo2 caused by activation of classical Wnt signaling are associated with osteoarthritis. Using the drug repositioning (DR) method based on the off-label effects of existing drugs, we searched for drugs that inhibit the progression of osteoarthritis by suppressing Rspo2, and found that the antidepressant Mianserin regulates the proliferative differentiation of chondrocytes by Rspo2. Next, we prepared a rat model of medial meniscectomy and administered mianserin intra-articularly to the rats, and histological analysis showed that the progression of osteoarthritis was inhibited.
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Academic Significance and Societal Importance of the Research Achievements |
既存薬のオフラベル効果による変形性関節症の治療薬の報告は少なく、本研究によって抗うつ剤であるMianserinが変形性関節症の進行予防効果を有する可能性について明らかとすることにできた。本研究の成果をもってMianserinによる関節症進行予防のヒトへの投与を含めた検討が可能となる。また、古典的Wntシグナルおよびそのシグナルを活性化させるRspo2が軟骨細胞に影響を与えることも同時に明らかとした。今後このシグナルをターゲットとしたさらなる研究をすすめることができる
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Report
(4 results)
Research Products
(19 results)