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Inhibiting myostatin signaling partially mitigates structural and functional adaptations to hindlimb suspension in mice.
Hanson, Andrea M; Young, Mary H; Harrison, Brooke C; Zhou, Xiaolan; Han, H Q; Stodieck, Louis S; Ferguson, Virginia L.
Affiliation
  • Hanson AM; Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, CO, USA.
  • Young MH; Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, CO, USA.
  • Harrison BC; Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA.
  • Zhou X; Amgen Inc., Thousand Oaks, CA, USA.
  • Han HQ; AliveGen USA Inc., Thousand Oaks, CA, USA.
  • Stodieck LS; Amgen Inc., Thousand Oaks, CA, USA.
  • Ferguson VL; AliveGen USA Inc., Thousand Oaks, CA, USA.
NPJ Microgravity ; 9(1): 2, 2023 Jan 16.
Article in En | MEDLINE | ID: mdl-36646717
ABSTRACT
Novel treatments for muscle wasting are of significant value to patients with disease states that result in muscle weakness, injury recovery after immobilization and bed rest, and for astronauts participating in long-duration spaceflight. We utilized an anti-myostatin peptibody to evaluate how myostatin signaling contributes to muscle loss in hindlimb suspension. Male C57BL/6 mice were left non-suspended (NS) or were hindlimb suspended (HS) for 14 days and treated with a placebo vehicle (P) or anti-myostatin peptibody (D). Hindlimb suspension (HS-P) resulted in rapid and significantly decreased body mass (-5.6% by day 13) with hindlimb skeletal muscle mass losses between -11.2% and -22.5% and treatment with myostatin inhibitor (HS-D) partially attenuated these losses. Myostatin inhibition increased hindlimb strength with no effect on soleus tetanic strength. Soleus mass and fiber CSA were reduced with suspension and did not increase with myostatin inhibition. In contrast, the gastrocnemius showed histological evidence of wasting with suspension that was partially mitigated with myostatin inhibition. While expression of genes related to protein degradation (Atrogin-1 and Murf-1) in the tibialis anterior increased with suspension, these atrogenes were not significantly reduced by myostatin inhibition despite a modest activation of the Akt/mTOR pathway. Taken together, these findings suggest that myostatin is important in hindlimb suspension but also motivates the study of other factors that contribute to disuse muscle wasting. Myostatin inhibition benefitted skeletal muscle size and function, which suggests therapeutic potential for both spaceflight and terrestrial applications.

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials Language: En Journal: NPJ Microgravity Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials Language: En Journal: NPJ Microgravity Year: 2023 Document type: Article Affiliation country: