ID | 63177 |
フルテキストURL | |
著者 |
Takemoto, Genta
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine
Matsushita, Masaki
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine
Okamoto, Takaaki
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine
Ito, Toshinari
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute
Matsuura, Yuki
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute
Takashima, Chieko
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute
Chen-Yoshikawa, Toyofumi Fengshi
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine
Ebi, Hiromichi
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute
Imagama, Shiro
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine
Kitoh, Hiroshi
Department of Orthopaedic Surgery, Aichi Children’s Health and Medical Center
Ohno, Kinji
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine
Hosono, Yasuyuki
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
researchmap
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抄録 | Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones.
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キーワード | FGFR3
achondroplasia
meclozine
zebrafish
bone
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発行日 | 2022-01-18
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出版物タイトル |
Frontiers In Cell And Developmental Biology
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巻 | 9巻
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出版者 | Frontiers Media SA
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開始ページ | 694018
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ISSN | 2296-634X
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2022 Takemoto, Matsushita, Okamoto, Ito, Matsuura, Takashima, Chen-Yoshikawa, Ebi, Imagama, Kitoh, Ohno and Hosono.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3389/fcell.2021.694018
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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Citation | Takemoto G, Matsushita M, Okamoto T, Ito T, Matsuura Y, Takashima C, Chen-Yoshikawa TF, Ebi H, Imagama S, Kitoh H, Ohno K and Hosono Y (2022) Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish. Front. Cell Dev. Biol. 9:694018. doi: 10.3389/fcell.2021.694018
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助成機関名 |
Japan Agency for Medical Research and Development
Japan Society for the Promotion of Science
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助成番号 | JP20ek0109414
JP21ek0109513
JP19K09646
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