Elucidation of the molecular basis of the bone-inducing factor NELL1
Project/Area Number |
17K01946
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biomolecular chemistry
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Research Institution | Nagoya University |
Principal Investigator |
Niimi Tomoaki 名古屋大学, 生命農学研究科, 講師 (30377791)
|
Project Period (FY) |
2017-04-01 – 2021-03-31
|
Project Status |
Discontinued (Fiscal Year 2020)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 骨分化 / 再生医療 / 骨形成 / 骨芽細胞 / 発生・分化 / シグナル伝達 |
Outline of Final Research Achievements |
The NELL1 gene was originally identified in craniosynostosis patients as being specifically upregulated within prematurely fusing sutures. Because of its potent osteoinductive activity, NELL1 protein may be useful for bone regeneration therapy. However, there is little knowledge regarding NELL1 receptors and NELL1-mediated signaling pathways. IAs a result of exploring the NELL1 receptor and elucidating the signal transduction mechanism, we identified Roundabout 2 (Robo2), which is mainly expressed in mesenchymal cells, as a novel receptor for NELL1. Furthermore, we elucidated the mode of ligand-receptor binding only under acidic conditions and suggested that it may act as a new bone formation signal.
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Academic Significance and Societal Importance of the Research Achievements |
骨再生・欠損修復製剤として欧米で承認されているBMPのような成長因子は分子量が30 k以下のサイトカインであるが、NELL1は3量体で400 kを超える巨大分子であり、分子の性状や局在においても大きく異なっている。このような新奇骨形成因子NELL1の受容体であるRobo2の同定と、酸性条件に特異的な結合様式の発見は、骨再生医療への応用の可能性を高め、さらに新たな創薬のターゲットとなることが期待される。
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Report
(4 results)
Research Products
(1 results)
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[Journal Article] Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/22019
Author(s)
Yamamoto, N., Kashiwagi, M., Ishihara, M., Kojima, T., Maturana, A. D., Kuroda, S., and Niimi, T.
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Journal Title
Journal of Biological Chemistry
Volume: 294
Issue: 12
Pages: 4693-4703
DOI
Related Report
Peer Reviewed