| Project/Area Number |
17K11005
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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 | Osaka University |
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Principal Investigator |
Kaito Takashi 大阪大学, 医学系研究科, 講師 (70623982)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 骨組織再生 / BMP-2 / 生体内イメージング / 異所性骨化 / BMP / PTH1-34 / Bisphosphonate / 骨芽細胞 / 破骨細胞 / Teriparatide / bone regeneration / ectopic bone formation / osteoblast / osteoclast / collagen / teriparatide / in vivo imaging |
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| Outline of Final Research Achievements |
Bone morphogenetic protein (BMP)-2 plays a central role in bone-tissue engineering because of its potent bone-induction ability. However, the process of BMP-induced bone formation in vivo remains poorly elucidated. In this study, we established a method for intravital imaging of the entire process of BMP-2-induced ectopic bone formation. Using multicolor intravital imaging in transgenic mice, we visualized the spatiotemporal process of bone induction, including appearance and motility of osteoblasts and osteoclasts, angiogenesis, collagen-fiber formation, and bone-mineral deposition. Furthermore, we investigated how PTH1-34 affects BMP-2-induced bone formation, which revealed that PTH1-34 administration accelerated differentiation and increased the motility of osteoblasts, whereas it decreased morphological changes in osteoclasts. This is the first report on visualization of the entire process of BMP-2-induced bone formation using intravital imaging techniques.
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| Academic Significance and Societal Importance of the Research Achievements |
外傷や腫瘍に伴う広範囲骨欠損の治療や脊椎固定術においては骨組織を早期に形成し骨癒合を獲得することが求められる。強力な骨形成能を有する骨形成因子（BMP）は欧米では広く臨床使用されるが、骨形成誘導過程に伴う炎症反応に関連した有害事象が多く報告されている。我々が確立したイメージング手法によりBMP-2誘導骨形成の最適化が可能となれば、BMP-2使用に関連する有害事象を低減しながら効率的な骨再生や骨癒合獲得期間を短縮できることが期待され、超高齢社会のなか骨癒合の獲得が一層容易ではなくなっている現在において、社会や医療経済的負担を低減することが期待される。
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