Elucidation of the mechanism of bone-resorption in osteoclasts regulated by Pkn3.
| Project/Area Number |
16K11494
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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 |
Functional basic dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小林 泰浩 松本歯科大学, 総合歯科医学研究所, 教授 (20264252)
細矢 明宏 北海道医療大学, 歯学部, 准教授 (70350824)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 破骨細胞 / 骨吸収 / Wnt非古典経路 / Pkn3 / 細胞骨格 / Wnt / Wnt5a / Rho |
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| Outline of Final Research Achievements |
Osteoclasts are responsible for bone resorption. In inflammatory disease such as arthritis and periodontitis leads to bone destruction due to the excess bone-resorbing activity of osteoclasts. We investigated roles of Wnt5a, a cytokine, in the osteoclast function. We have shown that Wnt5a-Ror2 signaling promotes osteoclast function through the activation of Daam2-Rho-protein kinase N3 (Pkn3)-c-Src signaling pathways.
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| Academic Significance and Societal Importance of the Research Achievements |
破骨細胞の機能を促進するメカニズムとして、Wnt5a-Ror2シグナルの下流で、Rho-Pkn3-c-Src経路が重要であることを明らかにした。破骨細胞の機能亢進は、骨粗鬆症や炎症性疾患（関節リウマチや歯周病）における骨破壊の進行に重要である。そのため、破骨細胞の機能を分子レベルで明らかにすることは、破骨細胞の機能を抑制する低分子の探索につながる。これにより、骨粗鬆症や炎症性骨破壊の新たな治療薬の開発が可能となる。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro.2017
Author(s)
Murakami K, Kobayashi Y, Uehara S, Suzuki T, Koide M, Yamashita T, Nakamura M, Takahashi N, Kato H, Udagawa N and Nakamura Y
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Journal Title
PLOS ONE
Volume: 12
Issue: 7
Pages: e0181126-e0181126
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling.2017
Author(s)
Uehara S, Udagawa N, Mukai H, Ishihara A, Maeda K, Yamashita T, Murakami K, Nishita M, Nakamura T, Kato S, Minami Y, Takahashi N and Kobayashi Y
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Journal Title
Sci Signal
Volume: 10
Issue: 494
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The HIV co-receptor CCR5 regulates osteoclast function.2017
Author(s)
Lee JW, Hoshino A, Inoue K, Saitou T, Uehara S, Kobayashi Y, Ueha S, Matsushima K, Yamaguchi A, Imai Y, Iimura T.
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Journal Title
Nat Commun
Volume: 8
Issue: 1
Pages: 2226-2226
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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