Analysis of the transcription factor Nfatc1 isoform in osteoclast differentiation
| Project/Area Number |
18K09118
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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 | Jichi Medical University (2019-2020)
Saitama Medical University (2018) |
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Principal Investigator |
Sato Kojiro 自治医科大学, 医学部, 教授 (10372434)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 破骨細胞 / Nfatc1 / RANKL / M-CSF / 骨芽細胞 / 滑膜線維芽細胞 / 関節リウマチ / 転写因子 |
|---|
| Outline of Final Research Achievements |
It is known that the expression level of a transcription factor Nfatc1 increases drastically in the process of osteoclast differentiation. At least three isoforms are expressed in osteoclasts, among which the shortest isoform increases in osteoclastogenesis. We have made this short isoform-specific knockout (KO) mice using CRISPR/Cas9 system. Homo KO mice are embryonic lethal, and TRAP-positive multi-nucleated cells do not differentiate from hematopoietic stem cells derived from KO fetuses, in contrast to those cells from wild type fetuses.
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| Academic Significance and Societal Importance of the Research Achievements |
この解析から、Nfatc1のbasalの発現だけではマウスは胎性致死に陥ることが判明した。肝臓における造血が不十分であることが一因であると思われる。また、より原始的な造血幹細胞から、単球系細胞は分化するものの破骨細胞は分化しないことから、Nfatc1のshort isoformの発現誘導が破骨細胞分化に必須であることが示された。今後このisoformの転写標的を同定する必要がある。本研究は破骨細胞や造血幹細胞の制御において有用な知見をもたらしつつある。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] <i>Salmonella enterica</i> Subspecies <i>arizonae</i> Detected from Bilateral Pleural Fluid in a Patient with Systemic Lupus Erythematosus and Malignant Lymphoma2020
Author(s)
Shima N, Nakamura J, Saito K, Kamata Y, Nagatani K, Nagashima T, Iwamoto M, Akine D, Saito T, Sato K, Minota S.
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Journal Title
Internal Medicine
Volume: 59
Issue: 9
Pages: 1223-1226
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2020-05-01
Related Report
Peer Reviewed
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[Journal Article] The correlation of urinary podocytes and podocalyxin with histological features of lupus nephritis.2018
Author(s)
Ikuma D, Hiromura K, Kajiyama H, Suwa J, Ikeuchi H, Sakairi T, Kaneko Y, Maeshima A, Kurosawa H, Hirayama Y, Yokota K, Araki Y, Sato K, Asanuma YF, Akiyama Y, Hara M, Nojima Y, Mimura T
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Journal Title
Lupus
Volume: 27
Issue: 3
Pages: 484-493
DOI
Related Report
Peer Reviewed
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