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
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.
