| Project/Area Number |
17K11034
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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 | Nihon University |
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Principal Investigator |
OSAKA Eiji 日本大学, 医学部, 准教授 (50468740)
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| Co-Investigator(Kenkyū-buntansha) |
穂坂 邦大 日本大学, 医学部, 兼任講師 (70570737)
徳橋 泰明 日本大学, 医学部, 教授 (80188739)
龍 啓之助 日本大学, 医学部, 専修指導医 (80837493)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 変形性関節症 / miRNA / 変形性膝関節症 / microRNA / 関節注射 / miR-218 / RUNX2 |
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| Outline of Final Research Achievements |
The expression of microRNAs (miRNAs) has been reported to be involved in the development and progression of osteoarthritis (OA) and has attracted much attention as a diagnostic marker and therapeutic target. miR-218 was shown to be significantly up-regulated in chondrocytes derived from OA patients compared to normal chondrocytes. We had also shown that overexpression or suppression of miR-218 regulated the expression of RUNX2 in normal chondrocytes. Furthermore, LPS-stimulated induction of normal chondrocytes resulted in concentration-dependent expression of miR-218 and RUNX2, while inhibition of miR-218 reduced RUNX2. These results suggest that targeting miR-218 in OA has the potential to prevent and improve OA progression.
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| Academic Significance and Societal Importance of the Research Achievements |
OAのmiR-218の調節によりRUNX2発現を制御しOAの進行、予防並びに改善の可能性があることが示唆された。しかしRUNX2はmiR-218の直接的な標的遺伝子であると報告されているが、骨肉腫ではにmiR-218過剰発現でRUNX2を発現抑制したのに対し本研究ではmiR-218過剰発現でRUNX2が過剰発現し、逆に抑制でRUNX2発現は抑制した。そのためmiR-218はRUNX2の直接的な標的遺伝子でない可能性もしくは骨肉腫とOAにおいては作用機序が異なる要素が関与している可能性がある。miR-218/RUNX2 axisには疾患特異的に複雑に介在するメカニズムがあるのではないかと考える。
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