title: Satellite cell dysfunction contributes to the progressive muscle atrophy in myotonic dystrophy type 1.
abstract: OBJECTIVE
  Myotonic dystrophy type 1 (DM1), one of the most common forms of inherited neuromuscular disorders in the adult, is characterized by progressive muscle weakness and wasting leading to distal muscle atrophy whereas proximal muscles of the same patients are spared during the early phase of the disease. In this report, the role of satellite cell dysfunction in the progressive muscular atrophy has been investigated.
  
  
  METHODS
  Biopsies were obtained from distal and proximal muscles of the same DM1 patients. Histological and immunohistological analyses were carried out and the past regenerative history of the muscle was evaluated. Satellite cell number was quantified in vivo and proliferative capacity was determined in vitro.
  
  
  RESULTS
  The size of the CTG expansion was positively correlated with the severity of the symptoms and the degree of muscle histopathology. Marked atrophy associated with typical DM1 features was observed in distal muscles of severely affected patients whereas proximal muscles were relatively spared. The number of satellite cells was significantly increased (twofold) in the distal muscles whereas very little regeneration was observed as confirmed by telomere analyses and developmental MyHC staining (0.3-3%). The satellite cells isolated from the DM1 distal muscles had a reduced proliferative capacity (36%) and stopped growing prematurely with telomeres longer than control cells (8.4 vs. 7.1 kb), indicating that the behaviour of these precursor cells was modified.
  
  
  CONCLUSIONS
  Our results indicate that alterations in the basic functions of the satellite cells progressively impair the muscle mass maintenance and/or regeneration resulting in gradual muscular atrophy.
authors.affiliation: Department of Integrative Medical Biology, Umea University, Sweden.
authors.forename: L-E
authors.initials: LE
authors.lastname: Thornell
authors.forename: M
authors.initials: M
authors.lastname: Lindstöm
authors.forename: V
authors.initials: V
authors.lastname: Renault
authors.forename: A
authors.initials: A
authors.lastname: Klein
authors.forename: V
authors.initials: V
authors.lastname: Mouly
authors.forename: T
authors.initials: T
authors.lastname: Ansved
authors.forename: G
authors.initials: G
authors.lastname: Butler-Browne
authors.forename: D
authors.initials: D
authors.lastname: Furling
mesh_terms: D000328:Adult; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009223:Myotonic Dystrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012038:Regeneration / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology / Q000502:physiology*; D012720:Severity of Illness Index; D016615:Telomere / Q000502:physiology; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases