| Project/Area Number |
18K09091
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
津田 英一 弘前大学, 医学研究科, 教授 (00361014)
木村 由佳 弘前大学, 医学研究科, 講師 (40455746)
佐々木 英嗣 弘前大学, 医学研究科, 助教 (60587038)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 再生医療 / 膝関節 / 軟骨 / 靱帯 / 半月板 / 変形性関節症 / スポーツ医学 / 前十字靭帯 / 再生医療 スポーツ医学 膝関節 前十字靭帯 / 前十字靱帯 / 再生誘導 / 修復 |
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| Outline of Final Research Achievements |
We investigated whether intra-articular tissue damage, which does not easily heal spontaneously, can be repaired using a regeneration induction technique. We created a mouse model with osteochondral defects and administered HMGB-1 (high mobility group box-1 protein) peptide or saline (control group). Although the cartilage defect was repaired with fibrous tissue in the control group, it was repaired with hyaline cartilage in the HMGB-1 group. In the parabiosis model with cartilage defects, it was demonstrated that the administration of HMGB1 facilitates transmigration of bone marrow mesenchymal stem cells into the cartilage defects through blood circulation. Currently, similar experiments for meniscus and anterior cruciate ligament injuries are ongoing. Based on these results, we have started a physician-led clinical trial to evaluate the safety of HMGB1 administration for osteoarthritis of the knee.
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| Academic Significance and Societal Importance of the Research Achievements |
HMGB-1（high mobility group box-1 protein）は核内遺伝子発現調節タンパクであり、重度の生体組織損傷時に血中に放出され骨髄由来間葉系幹細胞を血中へ動員する。しかし同時に全身性炎症も惹起するため、既知の炎症関連ドメインを排除したshort length HMGB-1 peptideを共同研究者の玉井らが開発した。今回の動物実験からその関節軟骨治癒促進効果が確認され、現在、変形性膝関節症に対する医師主導治験を開始している。HMGB-1が実用化されれば、本邦で2500万人といわれる変形性膝関節症患者のdisease modifying drugとなる。
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