Establishment of a novel sarcopenia mouse model by reducing serum IGF1 and development of a way for sarcopenia treatment by using the model
Project/Area Number |
19K09580
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Keio University |
Principal Investigator |
SATO Yuiko 慶應義塾大学, 医学部(信濃町), 研究員 (70445443)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | サルコペニア / 整形外科 |
Outline of Research at the Start |
筋力・筋量低下によるサルコペニアは高齢者の運動機能の低下や自立性の低下に直結するため、対策が必要です。アダルトにおいて血中のinsulin like growth factor 1 (IGF1)の濃度が減少するマウスモデル(IGF1 cKO)の作出に世界に先駆けて成功したので、本研究ではIGF1 cKOを用いて、IGF1による筋力・筋量制御機構の解明と、IGF1低下による筋力・筋量低下に対する対策法の開発を試みます。
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Outline of Final Research Achievements |
In this study, we established a novel mouse model (IGF1 conditional knockout, IGF1 cKO), in which its serum IGF1 levels were down-regulated to about half to those of control mice in adults. In IGF1 cKO mice, both muscle volume and power were significantly decreased compared with control mice, phenotypes mimic to sarcopenia patients. We found that decreased muscle volume was due to muscle atrophy in IGF1 cKO mice. In those atrophied muscles, expression levels of both anabolic and catabolic factors were decreased, suggesting that muscles underwent to metabolically a low turnover state under an IGF1 reduced condition in IGF1 cKO mice. Taken together, our results suggest that maintaining serum IGF1 levels is required to prevent sarcopenia development.
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Academic Significance and Societal Importance of the Research Achievements |
サルコペニアは加齢性に筋量と筋力が共に低下する退行性疾患であり、加齢を背景にした多因子疾患であると考えられていた。今回申請者はIGF1という単一の因子の血中濃度の低下のみによってサルコペニア様の表現型を若年齢のマウスにおいても発症し得る知見を得た。このことはサルコペニアの病態や発症要因を理解する上で重要な知見であり、学術的に意義がある。また、今回のモデルマウスではコントロールマウスの約半分の濃度にIGF1レベルを低下させているが、これはまさに人でも高齢者では若年者に比べて血中IGF1レベルが約1/2に低下することが知られており、本知見の人への応用という意味でも社会的意義も大きいと考えている。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice2021
Author(s)
Ito E, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Soma T, Matsumoto T, Kimura A, Miyamoto K, Matsumoto H, Matsumoto M, Nakamura M, Sato K, Miyamoto T
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Journal Title
Biochem Biophys Res Commun
Volume: 542
Pages: 48-53
DOI
Related Report
Peer Reviewed
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[Journal Article] Food restriction reduces cortical bone mass and serum insulin-like growth factor-1 levels and promotes uterine atrophy in mice2021
Author(s)
Ito E, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Soma T, Matsumoto T, Kimura A, Miyamoto K, Matsumoto H, Matsumoto M, Nakamura M, Sato K, Miyamoto T
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Journal Title
Biochem Biophys Res Commun
Volume: 534
Pages: 165-171
DOI
Related Report
Peer Reviewed
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[Journal Article] Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw2020
Author(s)
Soma T, Iwasaki R, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Ito E, Okada H, Watanabe H, Miyamoto K, Matsumoto M, Nakamura M, Asoda S, Kawana H, Nakagawa T, Miyamoto T
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Journal Title
J Bone Miner Metab
Volume: -
Issue: 3
Pages: 372-384
DOI
Related Report
Peer Reviewed
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[Journal Article] Smoking cessation increases levels of osteocalcin and uncarboxylated osteocalcin in human sera2020
Author(s)
Kiyota Y, Muramatsu H, Sato Y, Kobayashi T, Miyamoto K, Iwamoto T, Matsumoto M, Nakamura M, Tateno H, Sato K, Miyamoto T
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Journal Title
Sci Rep
Volume: 10
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Vitamin D protects against immobilization-induced muscle atrophy via neural crest-derived cells in mice2020
Author(s)
Nakamura S, Sato Y, Kobayashi T, Kaneko Y, Ito E, Soma T, Okada H, Miyamoto K, Oya A, Matsumoto M, Nakamura M, Kanaji A, Miyamoto T
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Journal Title
Sci Rep
Volume: 10
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.2019
Author(s)
Kaneko Y, Tanigawa N, Sato Y, Kobayashi T, Nakamura S, Ito E, Soma T, Miyamoto K, Kobayashi S, Harato K, Matsumoto M, Nakamura M, Niki Y, Miyamoto T.
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Journal Title
Sci Rep.
Volume: 9
Issue: 1
Pages: 18741-18741
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CTLA4-Ig directly inhibits osteoclastogenesis by interfering with intracellular calcium oscillations in bone marrow macrophages.2019
Author(s)
Okada H, Kajiya H, Omata Y, Matsumoto T, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Nakamura S, Koyama T, Sudo S, Shin M, Okamoto F, Watanabe H, Tachibana N, Hirose J, Saito T, Takai T, Matsumoto M, Nakamura M, Okabe K, Miyamoto T, Tanaka S.
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Journal Title
J Bone Miner Res
Volume: 34
Issue: 9
Pages: 1744-1752
DOI
Related Report
Peer Reviewed
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[Journal Article] Insulin-like growth factor-I is required to maintain muscle volume in adult mice.2019
Author(s)
Nakamura S, Sato Y, Kobayashi T, Oike T, Kaneko Y, Miyamoto K, Funayama A, Oya A, Nishiwaki T, Matsumoto M, Nakamura M, Kanaji A, Miyamoto T.
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Journal Title
J Bone Miner Metab.
Volume: 印刷中
Issue: 4
Pages: 627-635
DOI
Related Report
Peer Reviewed