start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=2 article-no= start-page=76 end-page=78 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Zebrafish models for cancer research kn-title=ƒ[ƒuƒ‰ƒtƒBƒbƒVƒ…‚π—p‚’‚½‚ͺ‚ρŒ€‹† en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name=Χ–μΛ”V kn-aut-sei=Χ–μ kn-aut-mei=Λ”V aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=‰ͺŽR‘εŠwŠwpŒ€‹†‰@ˆγŽ•–ςŠwˆζ@–ς—Šw en-keyword=zebrafish kn-keyword=zebrafish en-keyword=cancer kn-keyword=cancer en-keyword=drug development kn-keyword=drug development END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=694018 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish en-subtitle= kn-subtitle= en-abstract= kn-abstract=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. en-copyright= kn-copyright= en-aut-name=TakemotoGenta en-aut-sei=Takemoto en-aut-mei=Genta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsushitaMasaki en-aut-sei=Matsushita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoTakaaki en-aut-sei=Okamoto en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoToshinari en-aut-sei=Ito en-aut-mei=Toshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraYuki en-aut-sei=Matsuura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashimaChieko en-aut-sei=Takashima en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Chen-YoshikawaToyofumi Fengshi en-aut-sei=Chen-Yoshikawa en-aut-mei=Toyofumi Fengshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EbiHiromichi en-aut-sei=Ebi en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ImagamaShiro en-aut-sei=Imagama en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitohHiroshi en-aut-sei=Kitoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhnoKinji en-aut-sei=Ohno en-aut-mei=Kinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Division of Molecular Therapeutics, Aichi Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Aichi Childrenfs Health and Medical Center kn-affil= affil-num=11 en-affil=Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FGFR3 kn-keyword=FGFR3 en-keyword=achondroplasia kn-keyword=achondroplasia en-keyword=meclozine kn-keyword=meclozine en-keyword=zebrafish kn-keyword=zebrafish en-keyword=bone kn-keyword=bone END