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j.stemcr.2018.10.007.pdf | 13.69 MB | Adobe PDF | 見る/開く |
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DCフィールド | 値 | 言語 |
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dc.contributor.author | Hino, Kyosuke | en |
dc.contributor.author | Zhao, Chengzhu | en |
dc.contributor.author | Horigome, Kazuhiko | en |
dc.contributor.author | Nishio, Megumi | en |
dc.contributor.author | Okanishi, Yasue | en |
dc.contributor.author | Nagata, Sanae | en |
dc.contributor.author | Komura, Shingo | en |
dc.contributor.author | Yamada, Yasuhiro | en |
dc.contributor.author | Toguchida, Junya | en |
dc.contributor.author | Ohta, Akira | en |
dc.contributor.author | Ikeya, Makoto | en |
dc.contributor.alternative | 日野, 恭介 | ja |
dc.contributor.alternative | 趙, 成珠 | ja |
dc.contributor.alternative | 堀込, 一彦 | ja |
dc.contributor.alternative | 西尾, 恵 | ja |
dc.contributor.alternative | 岡西, 泰永 | ja |
dc.contributor.alternative | 永田, 早苗 | ja |
dc.contributor.alternative | 河村, 真吾 | ja |
dc.contributor.alternative | 山田, 泰広 | ja |
dc.contributor.alternative | 戸口田, 淳也 | ja |
dc.contributor.alternative | 太田, 章 | ja |
dc.contributor.alternative | 池谷, 真 | ja |
dc.date.accessioned | 2018-11-05T02:19:38Z | - |
dc.date.available | 2018-11-05T02:19:38Z | - |
dc.date.issued | 2018-11-13 | - |
dc.identifier.issn | 2213-6711 | - |
dc.identifier.uri | http://hdl.handle.net/2433/234940 | - |
dc.description | FOPにおける骨化を抑える新たな候補物質の同定 --治療法探索へ新しい戦略への可能性を拓く--. 京都大学プレスリリース. 2018-11-02. | ja |
dc.description.abstract | Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disorder characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor gain-of-function mutations in ACVR1 (FOP-ACVR1), a type I receptor for bone morphogenetic proteins. Despite numerous studies, no drugs have been approved for FOP. Here, we developed a high-throughput screening (HTS) system focused on the constitutive activation of FOP-ACVR1 by utilizing a chondrogenic ATDC5 cell line that stably expresses FOP-ACVR1. After HTS of 5, 000 small-molecule compounds, we identified two hit compounds that are effective at suppressing the enhanced chondrogenesis of FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and suppressed the heterotopic ossification (HO) of multiple model mice, including FOP-ACVR1 transgenic mice and HO model mice utilizing FOP-iPSCs. Furthermore, we revealed that one of the hit compounds is an mTOR signaling modulator that indirectly inhibits mTOR signaling. Our results demonstrate that these hit compounds could contribute to future drug repositioning and the mechanistic analysis of mTOR signaling. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | en |
dc.rights | © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | en |
dc.subject | mammalian target of rapamycin (mTOR) | en |
dc.subject | induced pluripotent stem cell (iPSC) | en |
dc.subject | fibrodysplasia ossificans progressiva (FOP) | en |
dc.subject | endochondral ossification | en |
dc.subject | heterotopic ossification | en |
dc.subject | bone morphogenetic protein (BMP) | en |
dc.subject | transforming growth factor β (TGF-β) | en |
dc.subject | activin A | en |
dc.subject | high-throughput screening (HTS) | en |
dc.subject | ACVR1 | en |
dc.title | An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Stem Cell Reports | en |
dc.identifier.volume | 11 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 1106 | - |
dc.identifier.epage | 1119 | - |
dc.relation.doi | 10.1016/j.stemcr.2018.10.007 | - |
dc.textversion | publisher | - |
dc.identifier.pmid | 30392977 | - |
dc.relation.url | https://www.kyoto-u.ac.jp/ja/research-news/2018-11-02 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 25293320 | - |
datacite.awardNumber | 16K15662 | - |
datacite.awardNumber | 17K15617 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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