Title

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight.

Document Type

Article

Publication Date

9-22-2020

Keywords

JGM

JAX Source

Proc Natl Acad Sci U S A 2020 Sep 22; 117(38):23942-23951

PMID

32900939

DOI

https://doi.org/10.1073/pnas.2014716117

Grant

UA-2019-031, AR060636,AG052962, Director's Innovation Fund from The Jackson Laboratory

Abstract

Among the physiological consequences of extended spaceflight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. Here, we used both genetic and pharmacological approaches to investigate the effect of targeting MSTN/activin A signaling in mice that were sent to the International Space Station. Wild type mice lost significant muscle and bone mass during the 33 d spent in microgravity. Muscle weights of Mstn -/- mice, which are about twice those of wild type mice, were largely maintained during spaceflight. Systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.

Comments

We thank Michael Roberts, Jennifer Finkel, William McLamb, Terri Bauer, Cole Nelson, Nicolas Cole, Raquel Jaeger, Melissa Rhodes, Alonso Fuentes, Hailey Willey, Jessica Gray, William Therrien, Kellie Leonard, Joe Bielitzki, Russell Higbee, Ramona Bober, Autumn Cdebaca, Mary Lou James, Grishma Acharya, Alixandra Borgert, Susie Airhart, and Sheila Bourgeois for all their help throughout this mission.

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