Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin

Hum Mol Genet. 2008 Dec 15;17(24):3975-86. doi: 10.1093/hmg/ddn301. Epub 2008 Sep 16.

Abstract

Myotendinous strain injury is the most common injury of human skeletal muscles because the majority of muscle forces are transmitted through this region. Although the immediate response to strain injury is well characterized, the chronic response to myotendinous strain injury is less clear. Here we examined the molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a microdystrophin transgene (microdystrophin(DeltaR4-R23)). We found that muscles with myotendinous strain injury had an increased expression of utrophin and alpha7-integrin together with the dramatic restructuring of peripheral myofibrils into concentric rings. The sarcolemma of the microdystrophin(DeltaR4-R23)/mdx gastrocnemius muscles was highly protected from experimental lengthening contractions, better than wild-type muscles. We also found a positive correlation between myotendinous strain injury and ringed fibers in the HSA(LR) (human skeletal actin, long repeat) mouse model of myotonic dystrophy. We suggest that changes in protein expression and the formation of rings are adaptations to myotendinous strain injury that help to prevent muscle necrosis and retain the function of necessary muscles during injury, ageing and disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / metabolism
  • Achilles Tendon / pathology*
  • Achilles Tendon / ultrastructure
  • Aging / genetics
  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Dystrophin / biosynthesis*
  • Dystrophin / genetics*
  • Dystrophin / physiology
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / ultrastructure
  • Muscular Dystrophy, Animal / genetics*
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Necrosis / genetics
  • Necrosis / prevention & control
  • Sprains and Strains / genetics
  • Sprains and Strains / metabolism
  • Sprains and Strains / pathology*

Substances

  • Dystrophin