Press Release

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

August 4, 2022

Abstract

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.

Journal Article

JOURNALBone Research

TITLE:Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling

DOIhttps://doi.org/10.1038/s41413-022-00225-w

Correspondence to

Tomoki NAKASHIMA, Professor

Department of Cell Signaling,
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University(TMDU)
E-mail:naka.csi(at)tmd.ac.jp

*Please change (at) in the e-mail addresses to @ when sending correspondence.