Journal article

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

Catherine E Winbanks, Justin L Chen, Hongwei Qian, Yingying Liu, Bianca C Bernardo, Claudia Beyer, Kevin I Watt, Rachel E Thomson, Timothy Connor, Bradley J Turner, Julie R McMullen, Lars Larsson, Sean L McGee, Craig A Harrison, Paul Gregorevic

JOURNAL OF CELL BIOLOGY | ROCKEFELLER UNIV PRESS | Published : 2013

Abstract

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 neuro..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by NHMRC


Awarded by Australian Research Council


Awarded by Honorary Senior Research Fellowship from the NHMRC


Funding Acknowledgements

This work was supported by project grant funding from the National Health and Medical Research Council (NHMRC) of Australia (526648 to P. Gregorevic, 1008910 to B. J. Turner, and 1006488 to C. A. Harrison), a Motor Neuron Disease Research Institute of Australia Mick Rodger Motor Neuron Disease research grant (B. J. Turner), and an initiation grant from the Swedish Foundation for International Cooperation in Research and Higher Education (L. Larsson and P. Gregorevic). C. A. Harrison is supported by a Career Development Fellowship (1013533) from the NHMRC. J. R. McMullen is supported by a Future Fellowship (FT0001657) from the Australian Research Council and an Honorary Senior Research Fellowship (586604) from the NHMRC. S. L. McGee is supported by a Career Development Fellowship (1030474) from the NHMRC. P. Gregorevic is supported by a Career Development Fellowship (1046782) from the NHMRC and, previously, a Senior Research Fellowship sponsored by Pfizer Australia. The Baker IDI Heart and Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government.