Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. C URRENT O PINION Bone and morphogenetic protein signalling and muscle mass Roberta Sartori a,b and Marco Sandri a,b,c Purpose of review The purpose of this study is to discuss the involvement of bone and morphogenetic proteins (BMPs) in the control of muscle mass. Recent findings The transforming growth factor-beta (TGFb) superfamily comprises a large number of secreted proteins that regulate a variety of fundamental biological processes. Sequence similarities define two ligand subfamilies: the TGFb/Activin subfamily and the BMP subfamily. Within the members of TGFb 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 TGFb 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 TGFb superfamily and its involvement in the homeostasis of adult muscle fibres. Summary The recent insights gained into the interplay of TGFb and BMP signalling in muscle have challenged our pre-existing ideas of how the adult skeletal muscle phenotype is regulated in health and disease. Keywords activin, bone and morphogenetic protein, MUSA1, muscle atrophy, muscle hypertrophy, myostatin, Smad INTRODUCTION Skeletal muscle mass and muscle fibre size may vary according to physiological and pathological con- ditions. An increase in muscle mass and fibre size, that is muscle growth or hypertrophy, occurs during development, in response to mechanical overload and/or anabolic hormonal stimulation. Cellular and protein turnover contribute to hypertrophy with different degree. During development and in early postnatal life, the growth of skeletal muscle, such as the mass of any other tissue, depends primarily on cellular turnover and secondarily on protein syn- thesis [1]. Conversely, in adulthood, the regulation of muscle mass and fibre size essentially reflects protein turnover, namely the balance between protein synthesis and degradation within the muscle fibres [2]. One of the most important anabolic signal is the insulin-like growth factor 1 (IGF1)-phosphoinositide-3-kinase (PI3K)-AKT/pro- tein kinase B (PKB) pathway that controls both protein synthesis and protein degradation. IGF1- Akt promotes not only muscle growth but also prevents muscle atrophy during catabolic conditions. Many signals coming from integrins and extracellular matrix, sex hormones, beta adre- nergic stimulation, nutrients, energy levels and inflammation with inflammatory cytokines con- verge on this pathway. One of the upstream signals that has been reported to impinge on IGF/AKT signal and that exerts a great effect on muscle mass regulation is the transforming growth factor-beta (TGFb) signalling. Myostatin is the most famous member of TGFb superfamily and myostatin inhi- bition leads to a massive muscle growth that, how- ever only partially depends on IGF1/AKT axis. Recent data on bone and morphogenetic proteins a Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, b Department of Biomedical Sciences, University of Padova, Padova and c Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy Correspondence to Marco Sandri, Department of Biomedical Sciences, University of Padova, Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine (VIMM), Viale Orus 2 35129 Padova, Italy. Tel: +39 049 7923258; fax: +39 049 7923250; e-mail: marco.sandri@unipd.it Curr Opin Clin Nutr Metab Care 2015, 18:215–220 DOI:10.1097/MCO.0000000000000172 1363-1950 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-clinicalnutrition.com REVIEW