mcgee-thebone-2013.pdf (3.72 MB)
The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass
journal contribution
posted on 2013-01-01, 00:00 authored by C Winbanks, J Chen, H Qian, Y Liu, B Bernardo, C Beyer, K Watt, R Thomson, Timothy ConnorTimothy Connor, B Turner, J McMullen, L Larsson, Sean McgeeSean Mcgee, C Harrison, P GregorevicAlthough the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.
History
Journal
The Journal of Cell BiologyVolume
203Issue
2Pagination
345 - 357Publisher
Rockefeller University PressLocation
New York, NYPublisher DOI
ISSN
1540-8140Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2013, Rockefeller University PressUsage metrics
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