Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies

Simon Hauerslev, Marie Louise Sveen, Morten Duno, Corrado Angelini, John Vissing, Thomas O. Krag

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration. Methods. We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD) with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC), vimentin, MyoD and myogenin and counting internally nucleated fibers. Results: We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the CAPN3 gene. Conclusions: Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.

Original languageEnglish
Article number43
JournalBMC Musculoskeletal Disorders
Volume13
DOIs
Publication statusPublished - 2012

Keywords

  • Calpain 3
  • INF
  • Limb girdle muscular dystrophy
  • Muscle regeneration
  • Neonatal myosin heavy chain
  • Vimentin

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rheumatology

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