Bone and morphogenetic protein signalling and muscle mass.

Abstract

The purpose of this study is to discuss the involvement of bone and morphogenetic proteins (BMPs) in the control of muscle mass. The transforming growth factor-beta (TGFβ) superfamily comprises a large number of secreted proteins that regulate a variety of fundamental biological processes. Sequence similarities define two ligand subfamilies: the TGFβ/Activin subfamily and the BMP subfamily. Within the members of TGFβ subfamily, myostatin emerged as the most critical ligand that affects muscle size and function. Indeed, mutations that inactivate Myostatin lead to important muscle growth in animals and humans. However, recent findings have increased the complexity of the TGFβ superfamily. Indeed, two independent groups have shown that BMP pathway, acting through Smad1/5/8, is the fundamental hypertrophic signal and dominates Myostatin signalling. Moreover, BMP-Smad1/5/8 negatively regulates a novel ubiquitin ligase, named MUSA1 that is required for muscle loss. This article reviews the rapid progress made in the last year regarding the signalling downstream TGFβ superfamily and its involvement in the homeostasis of adult muscle fibres. The recent insights gained into the interplay of TGFβ and BMP signalling in muscle have challenged our pre-existing ideas of how the adult skeletal muscle phenotype is regulated in health and disease.