Inhibition of myostatin prevents microgravity-induced loss of skeletal muscle mass and strength.

Autor: Smith RC; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Cramer MS; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Mitchell PJ; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Lucchesi J; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Ortega AM; Dept. of Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, Colorado, United States of America., Livingston EW; Dept. of Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina, United States of America., Ballard D; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Zhang L; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Hanson J; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Barton K; TechShot, Inc., Greenville, Indiana, United States of America., Berens S; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Credille KM; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Bateman TA; Dept. of Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina, United States of America., Ferguson VL; Dept. of Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, Colorado, United States of America.; Dept. of Mechanical Engineering, University of Colorado, Boulder, Colorado, United States of America., Ma YL; Lilly Research Laboratories, Indianapolis, Indiana, United States of America., Stodieck LS; Dept. of Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, Colorado, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Apr 21; Vol. 15 (4), pp. e0230818. Date of Electronic Publication: 2020 Apr 21 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0230818
Abstrakt: The microgravity conditions of prolonged spaceflight are known to result in skeletal muscle atrophy that leads to diminished functional performance. To assess if inhibition of the growth factor myostatin has potential to reverse these effects, mice were treated with a myostatin antibody while housed on the International Space Station. Grip strength of ground control mice increased 3.1% compared to baseline values over the 6 weeks of the study, whereas grip strength measured for the first time in space showed flight animals to be -7.8% decreased in strength compared to baseline values. Control mice in space exhibited, compared to ground-based controls, a smaller increase in DEXA-measured muscle mass (+3.9% vs +5.6% respectively) although the difference was not significant. All individual flight limb muscles analyzed (except for the EDL) weighed significantly less than their ground counterparts at the study end (range -4.4% to -28.4%). Treatment with myostatin antibody YN41 was able to prevent many of these space-induced muscle changes. YN41 was able to block the reduction in muscle grip strength caused by spaceflight and was able to significantly increase the weight of all muscles of flight mice (apart from the EDL). Muscles of YN41-treated flight mice weighed as much as muscles from Ground IgG mice, with the exception of the soleus, demonstrating the ability to prevent spaceflight-induced atrophy. Muscle gene expression analysis demonstrated significant effects of microgravity and myostatin inhibition on many genes. Gamt and Actc1 gene expression was modulated by microgravity and YN41 in opposing directions. Myostatin inhibition did not overcome the significant reduction of microgravity on femoral BMD nor did it increase femoral or vertebral BMD in ground control mice. In summary, myostatin inhibition may be an effective countermeasure to detrimental consequences of skeletal muscle under microgravity conditions.
Competing Interests: The employment of authors [RCS, MSC, PJM, JL, DB, LZ, JH, SB, KMC, YLM, KB] at Eli Lilly and Company and TechShot Inc. does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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