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

First Author  Baranowski RW Year  2023
Journal  iScience Volume  26
Issue  7 Pages  107047
PubMed ID  37360691 Mgi Jnum  J:337443
Mgi Id  MGI:7495303 Doi  10.1016/j.isci.2023.107047
Citation  Baranowski RW, et al. (2023) Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target. iScience 26(7):107047
abstractText  We examined the effects of approximately 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 GSK3beta content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3beta 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.
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