2019 Fiscal Year Final Research Report
Development of new therapeutic drug for osteoarthritis by drug repositioning
| Project/Area Number |
17K11009
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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 | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大月 孝志 岡山大学, 保健学研究科, 非常勤研究員 (10534802)
稲垣 純子 岡山大学, 医歯薬学総合研究科, 助教 (90271056)
廣畑 聡 岡山大学, 保健学研究科, 教授 (90332791)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 変形性関節症 / ドラッグ・リポジショニング / 細胞外基質分解酵素 |
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| Outline of Final Research Achievements |
In this study, we focused on the EMC-degrading enzymes that are important for osteoarthritis, and sought to find compounds that can inhibit the destruction of cartilage matrix by inhibiting the synthesis of EMC-degrading enzymes. We screened 400 kinds of pilot libraries provided by RIKEN. Results of examining the effect of suppressing the expression of ECM-degrading enzymes compound X significantly suppressed the mRNA expression of four extracellular matrix degrading enzymes such as MMP3, MMP13, ADAMTS4, and ADAMTS9, which were induced by inflammation caused by the inflammatory cytokine IL-1β. It also significantly suppressed the expression of the enzyme COX2, which has a role in promoting inflammation.
It was considered that compound X may be effective in treating OA.
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| Free Research Field |
病態医化学
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症（OA）は過度の力学的ストレスや加齢変化によって，関節破壊が生じる慢性炎症性疾患である。軟骨が消失することで疼痛や可動域制限等が生じ，患者の生活の質を著しく低下させるため，社会的にも重要な課題である。しかし，有力な治療法に乏しく，痛み止めなどの対症療法にとどまっている。今本研究では４００の化合物ライブラリーをOUMS-27(軟骨肉腫)に添加し、細胞外基質分解酵素のMMP-13及びADAMTS4.9, COX-2のmRNA発現量をリアルタイム定量PCR法及びwestern blot法にて検討した。スクリーニング検索を行った結果、有力な候補化合物を3つ決定した。
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