| Project/Area Number |
20K18460
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
Jiang Qing 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (00790007)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Tem8 / Runx2 / chondrocyte / proliferation / apoptosis |
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| Outline of Research at the Start |
Tem8 is one of the Runx2 targets in chondrocytes. Overexpression of Tem8 in chondrocytes induced chondrocyte apoptosis and disturbed the development of cartilaginous structures. We will elucidate the roles of Tem8 in skeletal development and the pathway of the induction of apoptosis by Tem8.
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| Outline of Final Research Achievements |
In the search of Runx2 target genes in chondrocytes, we found that Tem8 expression is upregulated by Runx2. Tem8 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Tem8-/- mice. However, the limbs of Tem8-/- mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Tem8 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Tem8, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Tem8 causes chondrocyte apoptosis accompanied by matrix mineralization.
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| Academic Significance and Societal Importance of the Research Achievements |
Antxr1は、軟骨細胞の成熟や血管の軟骨侵入、骨形成細胞の分化に影響を及ぼさず、軟骨細胞の増殖を調節していることを明らかにした。さらに、軟骨細胞におけるAntxr1の2回の過発現は、明らかな軟骨細胞のアポトーシスを誘導するのに十分であり、これはカルシウムまたはリン酸塩の代謝に関連するメカニズムによって引き起こされる可能性がある。人間の遺伝疾患の研究では、Tem8の突然変異がGAPO症候群を引き起こすことがわかっている。そのため、生理的な骨の発達だけでなく、変形性関節炎やGAPO症候群などの骨の病気のメカニズム解明にも役立つ。
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