| Project/Area Number |
18K09509
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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 57010:Oral biological science-related
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中富 満城 九州歯科大学, 歯学部, 講師 (10571771)
古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899)
自見 英治郎 九州大学, 歯学研究院, 教授 (40276598)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 破骨細胞 / Src / p130Cas / 骨吸収 / 骨代謝 |
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| Outline of Final Research Achievements |
Actin ring formation in osteoclasts is essential structure for bone resorption. Osteoclasts lacking Src or its downstream proteins p130Cas could not form actin ring. We investigated the mechanism how regulates Src-p130Cas signaling regulates actin ring formation. First, we explore the target protein of Src-p130Cas with microarray analysis using Src deficient osteoclasts and p130Cas deficient osteoclasts. Then, we identified Kif1c that is less expressed in Src and p130Cas. We found the potential of Kif1c to regulate actin ring because of Kif1c localization in actin ring by immunostaining. To examine the function of Kif1c, we suppressed Kif1c expression by shRNA in osteoclasts. Osteoclasts lost actin ring formation by kif1c knock down. Interestingly, overexpression of Kif1c accelerates actin ring formation in p130Cas deficient osteoclasts. These results suggest that Kif1c works under the Src-p130Cas signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
近年の研究により破骨細胞を喪失させずに骨吸収機能を制御できれば有害事象の少ない代謝性骨疾患の治療法につながると考えられている。そこで申請者らは破骨細胞の生存とは関係なく骨吸収機能を強力に活性化するSrc-p130Casシグナル分子に着目した。Srcとp130Casは様々な生命現象にも重要であるため、治療標的とはなりにくい。そこで、本研究ではSrc-p130Casシグナルの下流分子を探索し、破骨細胞の骨吸収機能を担う新たな分子としてKif1cを同定した。これによりSrc-p130Casシグナルの解明による代謝性骨疾患治療法の開発の一助になると期待される。
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