Reloading Injury, Chronic Recovery, and Fiber Type Adaption of Mouse Soleus Muscle after Four Weeks of Hind Limb Suspension

Abstract

Disuse and unloading rapidly result in skeletal muscle atrophy, fiber type switch and dysfunction. The recovery from those conditions has broad physiological and medical significances. To understand the recovery process and the molecular adaptations in muscle reloading, mouse soleus muscles were studied after 4 weeks of hind limb-suspension and reloading for 3, 7, 15, 30, 45 and 60 days. The results showed that 4 weeks of unloading produced significant muscle atrophy and reductions of contractile force and fatigue tolerance, accompanied by switches of myosin isoforms from IIa to IIx and IIb, with no change in type I myosin, and to more low molecular weight fast troponin T splice forms. During reloading, soleus muscle mass, fiber size and contractile force gradually recovered and reached the control level by 15 days. The levels of type IIa, IIx and IIb myosins recovered at 15 days of reloading. However, fatigue tolerance and post fatigue force recovery showed a trend of worsening during this period with significantly inflammatory cell infiltration at 3 and 7 days, indicating reloading injuries. The reloading injury was accompanied by up-regulations of filamin-C and alpha-crystallin-B, which returned to control level after 30 days. During the course of slow recovery, we observed later increases of type I myosin expression and the number of type I fibers to levels significantly higher than that in normal adult mouse soleus muscle at 30 to 60 days of reloading, which may contribute to the recovery of fatigue tolerance. The data demonstrated the value of increased slow fiber contents as a secondary adaption to compensate for muscle reloading injury, serving as an indicator for monitoring muscle function during the chronic recovery from unloading and disuse conditions.