File:Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling.pdf
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DescriptionSimultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling.pdf |
English: Impaired locomotion has been extensively studied worldwide because those afflicted with it have a potential risk of becoming bedridden. Physical exercise at times can be an effective remedy for frailty, but exercise therapy cannot be applied in all clinical cases. Medication is safer than exercise, but there are no drugs that reinforce both muscle and bone when administered alone. Multiple medications increase the risk of adverse events; thus, there is a need for individual drugs targeting both tissues. To this end, we established a novel sequential drug screening system and identified an aminoindazole derivative, locamidazole (LAMZ), which promotes both myogenesis and osteoblastogenesis while suppressing osteoclastogenesis. Administration of this drug enhanced locomotor function, with muscle and bone significantly strengthened. Mechanistically, LAMZ induced Mef2c and PGC-1α in a calcium signaling–dependent manner. As this signaling is activated upon physical exercise, LAMZ mimics physical exercise. Thus, LAMZ is a promising therapeutic drug for locomotor diseases, including sarcopenia and osteoporosis. |
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Source | https://www.nature.com/articles/s41413-022-00225-w#rightslink |
Author | Takehito Ono, Ryosuke Denda, Yuta Tsukahara, Takashi Nakamura, Kazuo Okamoto, Hiroshi Takayanagi & Tomoki Nakashima |
doi:10.1038/s41413-022-00225-w
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current | 06:20, 22 October 2022 | 1,239 × 1,645, 14 pages (3.19 MB) | Koavf (talk | contribs) | Uploaded a work by Takehito Ono, Ryosuke Denda, Yuta Tsukahara, Takashi Nakamura, Kazuo Okamoto, Hiroshi Takayanagi & Tomoki Nakashima from https://www.nature.com/articles/s41413-022-00225-w#rightslink with UploadWizard |
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Publisher | Springer US |
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Software used | Springer |
File change date and time | 06:09, 3 August 2022 |
Date and time of digitizing | 12:21, 2 August 2022 |
Date metadata was last modified | 06:09, 3 August 2022 |
Copyright status | Copyrighted |
Identifier | doi:10.1038/s41413-022-00225-w |
Conversion program | iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) |
Encrypted | no |
Page size | 595.276 x 790.866 pts |
Version of PDF format | 1.4 |