title: Osteopontin is highly expressed in severely dystrophic muscle and seems to play a role in muscle regeneration and fibrosis.
abstract: OBJECTIVE
  To increase our understanding of profibrotic mechanisms in dystrophic muscle.
  
  
  RESULTS
  Extracellular matrix, fibrosis-related molecules and histopathology were assessed in skeletal muscle of patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy type 1A (MDC1A).Osteopontin expression was much higher in DMD and MDC1A than in BMD and control muscle. Osteopontin was expressed in mononuclear cell infiltrates, on some muscle fibre surfaces, in regenerating fibres, and in calcified fibres. In all pathological muscles, matrix metalloproteinase (MMP)-1 was increased around groups of fibres that were also characterized by absence of collagen 1. The amounts of MMP-2, MMP-9 and tissue inhibitor of MMP -1 transcripts were also increased, whereas their proteins were variably expressed in muscle fibres (surface or cytoplasm) and at foci of necrosis and regeneration. Inflammatory cells, fibroblasts and myofibroblasts were more numerous in DMD and MDC1A than in BMD muscle.
  
  
  CONCLUSIONS
  Several fibrosis-related factors are greatly altered in severely dystrophic skeletal muscle. Osteopontin was the most conspicuously upregulated, both as transcript and as protein, in muscle fibres and infiltrating cells, indicating an intimate involvement in fibrosis, and also in inflammation and muscle regeneration, although its precise roles in these processes remain to be elucidated.
authors.affiliation: Division of Neuromuscular Diseases and Neuroimmunology, Istituto Nazionale Neurologico C. Besta, Milano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Zanotti
authors.forename: Sara
authors.initials: S
authors.lastname: Gibertini
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Blasi
authors.forename: Cristina
authors.initials: C
authors.lastname: Cappelletti
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
mesh_terms: D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology*; D053495:Osteopontin / Q000032:analysis / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D053495:Osteopontin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9