Establishment of Pathological Model of Skeletal resistance to PTH in Uremia using iPS Cells
| Project/Area Number |
17K09737
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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 |
Kidney internal medicine
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
溝渕 正英 昭和大学, 医学部, 講師 (90465203)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 副甲状腺ホルモン / 尿毒症 / iPS細胞 / CKD-MBD / 骨代謝 / 腎不全 / ミネラル代謝 / 骨芽細胞 / 間葉系幹細胞 / 内科 / 腎臓内科学 / 骨・ミネラル代謝 |
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| Outline of Final Research Achievements |
Although the hyporesponsiveness of parathyroid hormone, that is a master regulator in the bone-mineral metabolism, to bone is a major factor contributing to CKD-MBD, its pathomechanism is still obscure.
In the present study, we attempted to elucidate the mechanism of the hyporesponsiveness of PTH to bone using iPS-derived bone cells. Unfortunately, we could not obtain stable yield of iPS-derived bone cells with consistent phenotype responsive to various stimuli. Therefore, alternatively, investigated whether uremic factors mimic decreased responsiveness of PTH to mesenchymal stem cell-derived osteoblastic-like bone cells. As a result, we found that there are similar properties in responsiveness to various stimuli, including phosphate load, calcium depletion, and active vitamin D treatment, between bone tissues in uremia and mesenchymal stem cell-derived osteoblasts bone cells from uremic animal models.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病では様々な骨・ミネラル代謝がみられ、骨病変だけでなく心血管障害などの合併症の発症や進展に関与しています。本研究では、疾患モデル動物や患者から作製したiPS細胞から骨細胞を誘導し、これらの異常の研究に有用なモデル構築を目的としました。しかしながら、安定したiPS細胞由来の骨細胞を作製が困難であったために、骨髄や末梢血中の間葉系幹細胞から骨細胞を誘導し、これを使用して腎障害における骨・ミネラル代謝異常の原因の一端を明らかにすることが出来ました。本研究は、従来、生体から骨を取り出して行っていた研究が、容易に採取可能な間葉系幹細胞由来の骨細胞を用いることにより可能であること示しました。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Cdc42 regulates cranial suture morphogenesis and ossification2019
Author(s)
Aizawa Ryo、Yamada Atsushi、Seki Tatsuaki、Tanaka Junichi、Nagahama Ryo、Ikehata Mikiko、Kato Tadashi、Sakashita Akiko、Ogata Hiroaki、Chikazu Daichi、Maki Koutaro、Mishima Kenji、Yamamoto Matsuo、Kamijo Ryutaro
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 512
Issue: 2
Pages: 145-149
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation2018
Author(s)
Ikehata M, Yamada A, Fujita K, Yoshida Y, Kato T, Sakashita A, Ogata H, Iijima T, Kuroda M, Chikazu D, Kamijo R.
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Journal Title
Biochem Biophys Res Commun
Volume: 印刷中
Issue: 3
Pages: 525-529
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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