| Project/Area Number |
22K16744
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Hisanaga Satoshi 熊本大学, 大学院生命科学研究部(医), 特任助教 (30827308)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 変形性膝関節症 / 小胞体ストレス / 軟骨細胞 |
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| Outline of Research at the Start |
本研究では、変形性膝関節症患者より採取した関節軟骨において、タンパクの折り畳みに重要な役割を果たす分子シャペロン群の遺伝子発現の解析を行う。また軟骨細胞およびラット変形性膝関節症モデルに対して、軟骨基質の折り畳みを補助する化学シャペロンを投与することで、軟骨基質の分泌が改善し軟骨変性が抑制できるかを検討する。
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| Outline of Final Research Achievements |
increased expression of molecular chaperone-related genes has been confirmed in cartilage from patients with osteoarthritis of the knee, and single-cell RNA sequencing identified the chondrocyte group involved in maintaining cellular homeostasis in a cluster close to normal cartilage, in which endoplasmic reticulum stress-related genes, including chaperones, were elevated. Furthermore, cell lineage analysis revealed a cell group in which endoplasmic reticulum stress-related genes were elevated during the process of progression from normal cartilage to OA cartilage, and in this cell group, expression of COL2A was reduced. In other words, during the transition from normal cartilage to OA cartilage, protein folding function is reduced, causing a decrease in the ability to produce extracellular matrix, suggesting that this is one of the factors contributing to the progression of OA.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症は高齢者の健康寿命の延伸を阻害する代表的な運動器疾患である。軟骨破壊の進行を抑制する原因療法の開発が急務となっており、そのためには軟骨変性病態の分子メカニズムの解明による治療標的分子の同定が不可欠である。今回正常軟骨が変性する過程で小胞体に負荷がかかり、病態進行の一因となっている可能性が示唆された。今後その過程での薬剤による小胞体の負荷の軽減により進行予防が期待できる可能性がある。
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