Roles of an atypical Wnt receptor, Ryk, for bone formation and mineral metabolism
Project/Area Number |
16K11493
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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 |
Research Field |
Functional basic dentistry
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Research Institution | Matsumoto Dental University |
Principal Investigator |
Nakamichi Yuko 松本歯科大学, 総合歯科医学研究所, 講師 (20350829)
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Co-Investigator(Kenkyū-buntansha) |
宇田川 信之 松本歯科大学, 歯学部, 教授 (70245801)
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Research Collaborator |
Mori Tomoki 松本歯科大学, 大学院生
Horibe Kanji 松本歯科大学, 助教 (70733509)
Kobayashi Yasuhiro 松本歯科大学, 総合歯科医学研究所, 教授 (20264252)
Arai Atsushi 松本歯科大学, 歯学部, 講師 (00532772)
Major Michael Ben University of North Carolina at Chapel Hill, Lineberger Cancer Center, Associate Professor
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | Ryk / 骨ミネラル代謝 / プロテオゲノミクス / VDR / プロテオミクス / Wnt / 骨芽細胞 / 骨細胞 / 歯髄細胞 |
Outline of Final Research Achievements |
WNT signaling regulates numerous biological processes throughout life of all animals. Ryk is a member of the Wnt receptors, but it is called as a heretical or an atypical receptor because it seems to regulate both canonical and non-canonical Wnt pathways. In this study, we elucidated roles of Ryk for bone and mineral metabolism by using Ryk conventional KO (KO) and conditional KO (cKO) mice lines that are established in our laboratory. Using two mesenchymal-specific Ryk cKO mice, we confirmed that Ryk enhances bone formation. In addition, we tried to identify osteotropic downstream molecules of Wnt3a (one of the Ryk ligands) in the oversea collaborator, the Major laboratory in UNC-CH. To this end, we established a functional genomic screening method with a gain-of-function approach (called Crispr-A) using a sensitive reporter system I made. We also performed Phospho-MS analysis.
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Academic Significance and Societal Importance of the Research Achievements |
最近、Wntシグナルが活性化している悪性腫瘍において、抗腫瘍免疫活性がWntシグナルにより抑制されているという報告が多数存在する。これはRyk が、癌治療の有望な分子標的であることを示す。本研究ではRykの骨代謝における役割と共に、Crispr-Aスクリーニングに用いるレポーターシステムの立ち上げに成功した。今後、Ryk シグナルのエフェクター分子が同定されれば、基礎生物学のブレイクスルーとなる。このエフェクター分子は骨形成促進薬となり得るばかりか、がん治療、歯科領域治療における分子標的にもなる可能性がある。将来的には、Rykを標的とした新規治療法の開発がもたらされることが期待される。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop2019
Author(s)
Agajanian MJ, Walker MP, Axtman AD, Ruela-de-Sousa RR, Serafin DS, Rabinowitz AD, Graham DM, Ryan MB, Tamir T, Nakamichi Y, Gammons MV, Bennett JM, Counago RM, Drewry DH, Elkins JM, Gileadi C, Gileadi O, Godoi PH, Kapadia N, Muller, Santiago A, Sorrell FJ, Wells CI, Fedorov O, Willson TM, Zuercher WJ, Major MB.
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Journal Title
Cell Reports
Volume: 26
Issue: 1
Pages: 79-93.e8
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The W9 peptide directly stimulates osteoblast differentiation via RANKL signaling.2017
Author(s)
Nakamura M, Nakamichi Y, Mizoguchi T, Koide M, Yamashita T, Ara T, Nakamura H, Penninger JM, Furuya Y, Yasuda H, and Udagawa N
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Journal Title
Journal of Oral Biosciences
Volume: 59
Issue: 3
Pages: 146-151
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] VDR in osteoblast-lineage cells primarily mediates a 1a,25(OH)2D3 derivative-induced increase in bone mass by suppressing bone resorption.2017
Author(s)
Nakamichi Y, Udagawa N, Horibe K, Mizoguchi T, Yamamoto Y, Nakamura T, Hosoya A, Kato S, Suda T, and Takahashi N.
Organizer
第20回ビタミンDワークショップ
Place of Presentation
Rosen Centre (米国フロリダ州オランド)
Year and Date
2017-03-28
Related Report
Int'l Joint Research
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[Presentation] ビタミンDの骨量増加の薬理作用は、破骨細胞ではなく骨芽細胞のVDRを介する2016
Author(s)
中道裕子,溝口利英, 山本陽子, 中村貴、細矢明宏, 堀部寛治, 原田卓, 斎藤一史, 加藤茂明, 須田立雄, 宇田川信之, 高橋直之
Organizer
第34回日本骨代謝学会学術集会
Place of Presentation
大阪国際会議場(大阪府大阪市)
Year and Date
2016-07-20
Related Report
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