2021 Fiscal Year Final Research Report
The role of chondrocyte/senescent cells-derived exosomal microRNA in pathogenesis of osteoarthritis, and in silico drug discoveryathogenesis of osteoarthritis and in silico drug discovery
| Project/Area Number |
19H03785
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
眞田 洋平 広島大学, 病院(医), 研究員 (50796117)
山西 芳裕 九州工業大学, 大学院情報工学研究院, 教授 (60437267)
中佐 智幸 広島大学, 病院(医), 講師 (60467769)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 変形性関節症 / microRNA / 細胞老化 / ドラックリポジショニング / 機械学習 |
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| Outline of Final Research Achievements |
Osteoarthritis (OA) is the most prevalent arthritic disease. The present study focused on the role of chondrocyte/senescent cells-derived cellular/exosomal microRNA in OA pathogenesis and in silico drug discovery for OA treatment. Although miR-23 a/b cluster and miR-26a were highly expressed in articular chondrocytes, both cellular and exsomal miRNAs (miR-23a/b and miR-26a) are not essential for OA pathogenesis associated with aging, and mechanical overload and local inflammation by trauma. However, both knock out mice exhibited accelerated aging-phenotype such as bone loss. Thus, we should further examine what function of these miRNAs including exosomal miRNAs is derived from which cells, and their target genes in order to reveal the mechanism of accelerated aging-like phenotype such as osteopenia in knock out mice. These future results might open a new insight in aging mechanisms through miR-23 a/b clusters and miR-26a.
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| Free Research Field |
軟骨代謝
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| Academic Significance and Societal Importance of the Research Achievements |
これまで in vitro 実験によりOAにおけるmiR-23a/bクラスターおよびmiR-26aの機能が報告されてきたが、議論の余地があった。本研究による遺伝子改変マウスの結果から、これらmiRNAは軟骨細胞で高発現しているものの、細胞内および分泌型miRNAとしてもOA発症に本質的な役割がないことを明らかにできた。さらに、これらmiRNAのノックアウトマウスは、骨密度の低下など老化様の表現系を示すことから、今後の研究によりmiR-23 a/bクラスターとmiR-26aを介した老化メカニズムの新しい洞察を開く可能性がある。また、未だ治療薬のないOAの治療薬を探索することには意義がある。
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