Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target

Ryan W. Baranowski; Jessica L. Braun; Briana L. Hockey; Jenalyn L. Yumol; Mia S. Geromella; Colton J.F. Watson; Nigel Kurgan; Holt N. Messner; Kennedy C. Whitley; Adam J. MacNeil; Guillemette Gauquelin-Koch; Fabrice Bertile; William Gittings; Rene Vandenboom; Wendy E. Ward; Val A. Fajardo

iScience (Jul 2023)

Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target

Ryan W. Baranowski,
Jessica L. Braun,
Briana L. Hockey,
Jenalyn L. Yumol,
Mia S. Geromella,
Colton J.F. Watson,
Nigel Kurgan,
Holt N. Messner,
Kennedy C. Whitley,
Adam J. MacNeil,
Guillemette Gauquelin-Koch,
Fabrice Bertile,
William Gittings,
Rene Vandenboom,
Wendy E. Ward,
Val A. Fajardo

Affiliations

Ryan W. Baranowski: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Jessica L. Braun: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Briana L. Hockey: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Jenalyn L. Yumol: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Mia S. Geromella: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Colton J.F. Watson: Department of Health Sciences, Brock University, St. Catharines, ON, Canada
Nigel Kurgan: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Holt N. Messner: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Kennedy C. Whitley: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Adam J. MacNeil: Department of Health Sciences, Brock University, St. Catharines, ON, Canada
Guillemette Gauquelin-Koch: French Space Agency, Centre National d'Etudes Spatiales (CNES), Paris, France
Fabrice Bertile: Hubert Curien Pluridisciplinary Institute (IPHC), CNRS, Strasbourg University, Strasbourg, France
William Gittings: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Rene Vandenboom: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Wendy E. Ward: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada
Val A. Fajardo: Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Corresponding author

Journal volume & issue: Vol. 26, no. 7
p. 107047

Abstract

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Summary: We examined the effects of ∼30 days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3β content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3β was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3. We then tested the effects of inhibiting GSK3 before this fiber type shift, and we demonstrate that muscle-specific Gsk3 knockdown increased muscle mass, preserved muscle strength, and promoted the oxidative fiber type with Earth-based hindlimb unloading. In bone, GSK3 activation was enhanced after spaceflight; and strikingly, muscle-specific Gsk3 deletion increased bone mineral density in response to hindlimb unloading. Thus, future studies should test the effects of GSK3 inhibition during spaceflight.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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