التفاصيل البيبلوغرافية
| العنوان: |
Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva |
| المؤلفون: |
Sun, Liping, Jin, Yonghui, Nishio, Megumi, Watanabe, Makoto, Kamakura, Takeshi, Nagata, Sanae, Fukuda, Masayuki, Maekawa, Hirotsugu, Kawai, Shunsuke, Yamamoto, Takuya, Toguchida, Junya |
| المساهمون: |
孫, 麗萍, 金, 永輝, 西尾, 恵, 渡辺, 真, 鎌倉, 武史, 永田, 早苗, 福田, 真幸, 前川, 裕継, 川井, 俊介, 山本, 拓也, 戸口田, 淳也, 90620344, 60546993 |
| بيانات النشر: |
Life Science Alliance, LLC |
| سنة النشر: |
2024 |
| المجموعة: |
Kyoto University Research Information Repository (KURENAI) / 京都大学学術情報リポジトリ |
| مصطلحات موضوعية: |
Cell Biology, Metabolism, Stem Cells |
| الوصف: |
酸化的リン酸化の抑制がFOPの新たな治療法に繋がる可能性. 京都大学プレスリリース. 2024-03-11. ; Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A–induced chondrogenesis of mesenchymal stem cells derived from FOP patient–specific induced pluripotent stem cells. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, along with increased mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, whereas OXPHOS inhibitor IACS-010759 inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury–induced enrichment of fibro/adipogenic progenitor genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
2575-1077 |
| العلاقة: |
https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/240311-150000.htmlTest; https://www.infront.kyoto-u.ac.jp/post-4920Test/; http://hdl.handle.net/2433/287382Test; Life Science Alliance; e202302219 |
| الإتاحة: |
http://hdl.handle.net/2433/287382Test |
| حقوق: |
© 2024 Sun et al. ; This article is available under a Creative Commons License (Attribution 4.0 International). ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.F3E09B0 |
| قاعدة البيانات: |
BASE |
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