The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

CE Winbanks, JL Chen, H Qian, Y Liu… - Journal of Cell …, 2013 - rupress.org
CE Winbanks, JL Chen, H Qian, Y Liu, BC Bernardo, C Beyer, KI Watt, RE Thomson
Journal of Cell Biology, 2013rupress.org
Although 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 …
Although 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.
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