Fig 1.
Effect of myostatin inhibition on muscle function and lean muscle mass under conditions of microgravity.
Grip strength (A) and lean muscle mass (B) were measured in Ground IgG, Ground YN41, Flight IgG and Flight YN41 groups at launch and weeks 4 and 6 post-launch, expressed as percent change from the same groups measured at baseline, with all baseline measurements having been made on the ground using Lunar PIXImus. (C) Representative mouse image from the DEXA densitometer showing the region of interest (ROI) of the hindlimb outlined in black used in panel B. (D) Carcass weights of all groups. Significance (p < 0.05 *, 0.001 **) for comparison to respective control IgG group or to Ground IgG group (p < 0.05 #, p < 0.001 ##) is noted.
Fig 2.
Effect of myostatin inhibition on muscle, brain and heart weights under conditions of microgravity.
Individual weights of (A) gastrocnemius, (B) quadriceps, (C) plantaris, (D) soleus, (E) heart, (F) brain for Ground IgG, Ground YN41, Flight IgG and Flight YN41 groups at weeks 4 and 6 post-launch expressed as % change from the baseline group (A-D) or absolute weight (E-F). *, ** Indicates significance vs. its respective IgG control; #, ## indicates significance vs. ground IgG. p < 0.05, p<0.001.
Table 1.
Effect of myostatin inhibition on individual muscle weights under conditions of microgravity.
Fig 3.
Effect of myostatin inhibition and microgravity on femoral head and muscle histology and myofiber size.
A). No degenerative or inflammatory changes were microscopically observed in observed in longitudinal sections of the femoral head near the ligament of the head of the femur (A) or in transverse sections of the lower hind limb muscles (B) in control or YN41 treated mice housed on the ground or in flight. i) Ground IgG, ii) Ground YN41, iii) Flight IgG, iv) Flight YN41. High magnification inset in B is of the soleus muscle (centrally located). (C). Mean cross-sectional areas of lower limb hindlimb muscle fibers from ground and flight groups, where two-way ANOVA showed main effects of both myostatin inhibition (p < 0.0001) and spaceflight (p < 0.05). **p<0.001 vs their respective IgG controls. D). Representative image of a lower limb muscle section (top) stained to highlight muscle fibers and its corresponding image analysis mask (bottom) used as part of the image analysis process.
Fig 4.
Effect of microgravity and myostatin inhibition on skeletal muscle gene expression.
Gene expression profiles of 8 genes in gastrocnemius (G), quadriceps (Q), soleus (S) and tibialis anterior (T) muscles of flight and ground animals. Significance at p<0.05, p<0.001 relative to the respective control groups (*,**), to the Flight IgG group (#,##) and to the Ground IgG group ($,$ $).
Fig 5.
Effect of microgravity and myostatin inhibition on bone density.
A. Areal bone mineral density measured in vivo by DEXA in Ground IgG, Ground YN41, Flight IgG and Flight YN41 groups at weeks 4 and 6 post-launch expressed as % change from the same groups measured at week 0. (*), refers to significance relative to its respective control at each time point. All p values < 0.05. BMD of distal (B) and mid (C) femurs as measured by ex vivo CT. * denotes significance to Ground IgG, p<0.05. Two-way ANOVA revealed significant main effects of spaceflight, but no significant effect of myostatin inhibition, for areal BMD at both 4 and 6 weeks post-launch (p < 0.01 and p < 0.0001, respectively) and BMD of distal and mid-femurs (p < 0.0001).
Table 2.
Age and microgravity, but not myostatin inhibition, influence vBMD in the femur but not the vertebrae.
Age and microgravity, but not myostatin inhibition, also influence both trabecular and cortical bone microarchitecture at the distal femur.
Fig 6.
Representative micro-computed tomography images from the distal femur from baselines as well as ground and flight mice treated with either IgG or YN41.
While visual differences between groups are subtle, the microarchitecture of both trabecular and cortical compartments significantly improved with skeletal maturation when comparing baseline to ground controls (IgG), and both bone compartments were significantly diminished with microgravity exposure (comparing IgG ground to flight groups) but were unaffected by myostatin inhibition.
Table 3.
Effect of microgravity and myostatin inhibition on femoral biomechanics.