Myosin Heavy Chain Expression in Skeletal Muscle Autografts under Neural or Aneural Conditions

Abstract

Background.Our purpose was to investigate (1) the heterogeneity of satellite cells derived from adult fast-twitch and slow-twitch skeletal muscles, (2) the influence of innervation on muscle regeneration, and (3) the differences between developmental myoblasts and satellite cells with regard to myosin heavy chain (MHC) expression.Materials and methods.Autografts under neural (nerve-intact graft;brief denervation interval) or aneural (aneural graft;prolonged denervation interval) conditions of the fast-twitch extensor digitorum longus (EDL) muscle or the slow-twitch soleus muscle were performed in adult rat hindlimbs. MHC expression during skeletal muscle regeneration was determined sequentially using immunocytochemistry.Results.After grafting, most muscle fibers in the EDL and soleus underwent ischemic degeneration and regeneration; at the periphery of each muscle, a few adult fibers survived. All regenerating fibers initially expressed embryonic/fetal (developmental) MHC alone, and subsequently both developmental and fast MHC. During the first week, no expression of slow MHC was observed in regenerating fibers in either the EDL or the soleus. In nerve-intact grafts, regenerating fibers expressed slow MHC as early as the second week; under aneural conditions, no regenerating fibers expressed slow MHC even 4 weeks after grafting. On the other hand, some persisting fibers in aneural grafts could maintain expression of slow MHC 4 weeks after grafting; other fibers underwent MHC transformation induced by denervation. No significant difference in MHC expression during regeneration was observed for slow compared with fast muscles, under either neural or aneural condition.Conclusions.These data suggest that regenerating adult skeletal muscle fibers, derived only from satellite cells, cannot express slow MHC without motor innervation, and that persisting muscle fibers, derived from both myoblasts in fetal development and satellite cells, may be intrinsically distinct from regenerating fibers. Satellite cells derived from slow and from fast muscles may be a single, homogenous population and may be the same population as fetal (secondary) myoblasts with regard to MHC expression.