Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1αsignaling

查看全文 作　　者：Takehito [1]Ono;Ryosuke [1,2]Denda;Yuta [1,3]Tsukahara;Takashi [4]Nakamura;Kazuo [5]Okamoto;Hiroshi [6]Takayanagi;Tomoki [1]Nakashima

机构地区：[1]Department of Cell Signaling,Graduate School of Medical and Dental Sciences,Tokyo Medical and Dental University(TMDU),Yushima 1-5-45,Bunkyo-ku,Tokyo 113-8549,Japan;[2]Department of Orthopaedic Surgery,The Jikei University School of Medicine,3-25-8 Nishi-Shimbashi,Minato-ku,Tokyo 105-8461,Japan;[3]School of Dentistry,Tokyo Medical and Dental University(TMDU),Yushima 1-5-45,Bunkyo-ku,Tokyo 113-8549,Japan;[4]Department of Biochemistry,Tokyo Dental College,Kandamisakicho 2-9-18,Chiyoda-ku,Tokyo 101-0061,Japan;[5]Department of Osteoimmunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Hongo 7-3-1,Bunkyo-ku,Tokyo 113-0033,Japan;[6]Department of Immunology,Graduate School of Medicine and Faculty of Medicine,The University of Tokyo,Hongo 7-3-1,Bunkyo-ku,Tokyo 113-0033,Japan

出　　处：《Bone Research》索引2022年第10卷第4期,共14页

基　　金：supported in part by the Japan Society for the Promotion of Science(JSPS);the Japan Science and Technology Agency;Daiichi Sankyo Company;Daiichi Sankyo Foundation of Life Science;Hisamitsu Pharmaceutical;Japan Rheumatism Foundation;the Life Science Foundation of Japan;Lotte Research Promotion Grant;Meiji Yasuda Life Foundation;Mitsui Life Social Welfare Foundation;Naito Foundation;Suzuken Memorial Foundation;Takeda Science Foundation;The Asahi Glass Foundation;The Sumitomo Foundation;The Uehara Memorial Foundation;Secom Science and Technology Foundation(SSTF). 摘　　要：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-1αin 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. 关键词：DRUGS clinical DISEASES

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Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1αsignaling

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