Development of bone regeneration methods based on understanding of tissue remodeling
| Project/Area Number |
21K19883
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Tei Yuichi 東京大学, 大学院工学系研究科(工学部), 教授 (30345053)
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| Co-Investigator(Kenkyū-buntansha) |
岡田 寛之 東京大学, 大学院医学系研究科(医学部), 助教 (10883481)
大庭 伸介 大阪大学, 大学院歯学研究科, 教授 (20466733)
酒井 崇匡 東京大学, 大学院工学系研究科(工学部), 教授 (70456151)
北條 宏徳 東京大学, 大学院医学系研究科(医学部), 准教授 (80788422)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 組織リモデリング / バイオマテリアル / 骨再生 / 線維化 / 一細胞解析 / 骨欠損 |
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| Outline of Research at the Start |
組織修復の理解には、組織リモデリングと呼ばれる、組織損傷部位における炎症・免疫反応の制御と、体制幹細胞の増殖・分化を介する組織再生の制御の両方が必要です。本研究では、この両制御機構を包括的に理解し、適切なバイオマテリアルと統合することで、組織リモデリングの制御に基づく新しい骨再生戦略の確立を目指します。
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| Outline of Final Research Achievements |
In this study, by focusing on skeletal progenitors, we performed the lineage tracing analysis and single cell RNA-seq (scRNA-seq) analysis to understand behavior of the progenitors and the mechanism of cell fate determination to osteoblasts at bone repair sites. As a result, we confirmed that Gli1-positive cells were activated at bone repair sites and contributed to bone repair and fibrosis. scRNA-seq analysis provided candidate signaling factors involved in the fate determination to osteoblasts. We also developed a new hydrogel with drug-loading ability and demonstrated its contribution to bone regeneration in cell experiments and animal models.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、骨の修復過程におけるGli1陽性の骨格系前駆細胞の振る舞いと、骨修復・線維化における制御機構の一端が明らかになった。一細胞解析により、骨再生への関与が推定される候補因子群が見つかった。さらに、新規ハイドロゲルの開発を通して、成長因子を保持・遊離可能な機構を有する足場材料の開発に成功した。今後、これらの因子・材料を組み合わせることで、安全で効率的な骨再生医療の実現に寄与することが期待される。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages2022
Author(s)
Hojo Hironori, Saito Taku, He Xinjun, Guo Qiuyu, Onodera Shoko, Azuma Toshifumi, Koebis Michinori, Nakao Kazuki, Aiba Atsu, Seki Masahide, Suzuki Yutaka, Okada Hiroyuki, Tanaka Sakae, Chung Ung-il, McMahon Andrew P., Ohba Shinsuke
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Journal Title
Cell Reports
Volume: 40
Issue: 10
Pages: 111315-111315
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development2022
Author(s)
Nagata K, Hojo H, Chang SH, Okada H, Chijimatsu R, Omata Y, Mori D, Makii Y, Kawata M, Kaneko T, Iwanaga Y, Nakamoto H, Maenohara Y, Tachibana N, Ishikura H, Higuchi J, Taniguchi Y, Ohba S, Chung Ul, Tanaka S, Saito T
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Journal Title
Nature Communications
Volume: 13
Issue: 1
Pages: 6187-6204
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin2021
Author(s)
Wang JS, Kamath T, Mazur CM, Mirzamohammadi F, Rotter D, Hojo H, Castro CD, Tokavanich N, Patel R, Govea N, Enishi T, Wu Y, da Silva Martins J, Bruce M, Brooks DJ, Bouxsein ML, Tokarz D, Lin CP, Abdul A, Macosko EZ, Fiscaletti M, Munns CF, Ryder P, Kost-Alimova M, Byrne P, Cimini B, Fujiwara M, Kronenberg HM, Wein MN.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 6271-6271
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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