| Project/Area Number |
17K17322
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthodontics/Pediatric dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
Takeuchi Yuto 大阪大学, 歯学部附属病院, 医員 (60721454)
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| Research Collaborator |
ABE makoto
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 骨・軟骨 / シグナル伝達 / 口腔解剖学 / 口腔生化学 / KLF4 / 歯学 / 解剖学 |
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| Outline of Final Research Achievements |
Based on various preliminary observations, I hypothesized that, a transcription factor, KLF4, play important roles during chondrocyte development and homeostasis. I initially precisely determined the protein localization site of KLF4 during endochondral ossification. KLF4 localized to the cells of prehypertrophic and hypertrophic zone. At embryonic stage, KLF4 was localized to articular chondrocytes but its expression diminished as joint matured. We showed that KLF4 strongly induces Mmp13 expression and protein level in chondrocytes. This upregulation of Mmp13 mRNA level was not due to increased rate of transcription, but due to deceased mRNA decay. We further found that KLF4 regulates primary cilia function in osteoblasts, another skeletal cells those play important roles for skeletal development and homeostasis. Through regulation of the primary cilium function, KLF4 modulated the Hedgehog signaling, and consequently osteoblast differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの骨格の大部分は、内軟骨骨化の過程で発生する。骨格に形態・性状異常を認める疾患は比較的多く、先天的な発生異常を示すものや後天的に骨の恒常性維持機構の破綻によるものなど多岐にわたる。手足の骨や関節は日常生活で最も使用される部位の一つであり、その異常は日々の動作に対して著しく大きな影響を与えることが容易に想定される。KLF4が内軟骨骨化の過程において果たす役割を解明することで、KLF4は骨格に異常をきたす疾患に対する創薬のターゲットとなりえる可能性がある。
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