한빛사 논문
The Jackson Laboratory for Genomic Medicine, University of Connecticut School of Medicine
Se-Jin Leea,b,1, Adam Lehara, Jessica U. Meirc, Christina Kochc, Andrew Morganc, Lara E. Warrend, Renata Rydzike, Daniel W. Youngstrome, Harshpreet Chandoka, Joshy Georgea, Joseph Gogainf, Michael Michauda, Thomas A. Stoklaseka, Yewei Liua, and Emily L. Germain-Leeg,h
aThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032; bDepartment of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT 06030; cThe National Aeronautics and Space Administration, NASA Johnson Space Center, Houston, TX 77058; dCenter for the Advancement of Science in Space, Houston, TX 77058; eDepartment of Orthopaedic Surgery, University of Connecticut School of Medicine, Farmington, CT 06030; fSomaLogic, Inc., Boulder, CO 80301; gDepartment of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030; and hConnecticut Children’s Center for Rare Bone Disorders, Farmington, CT 06032
1To whom correspondence may be addressed.
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.
myostatin, activin, skeletal muscle, bone, microgravity
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