Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway

• DOI: 10.1073/pnas.2111401118
• Publication Date: 2021-08-12T19:41:11Z
• Authors: Yewei Liu; Adam Lehar; Renata Rydzik; Harshpreet Chandok; Yun-Sil Lee; Daniel W. Youngstrom; Joshy George; Martin M. Matzuk; Emily L. Germain-Lee; Se-Jin Lee
• Keywords: Follistatin; Heterozygote; 0303 health sciences; Bone Development; JGM; Life Sciences; 610; Gene Expression Regulation, Developmental; Biological Sciences; Mice; 03 medical and health sciences; Gene Expression Regulation; Bone Density; Transforming Growth Factor beta; Multigene Family; Medicine and Health Sciences; Animals; Homeostasis; Muscle, Skeletal; Alleles; Signal Transduction

Significance Maintenance of skeletal muscle and bone is regulated by key signaling proteins belonging to the transforming growth factor family. Here, we present genetic studies in mice showing that follistatin, which normally blocks the activities of these proteins, acts locally in an exquisitely dose-dependent manner to control muscle and bone growth. Moreover, our studies targeting the receptors for these proteins reveal the enormous capacity for bone growth that is normally kept in check by this signaling system. These findings have implications for strategies to target this signaling pathway for clinical applications to treat patients with muscle and bone loss.