title: Increased collagen cross-linking is a signature of dystrophin-deficient muscle.
abstract: Collagen cross-linking is a key parameter in extracellular matrix (ECM) maturation, turnover, and stiffness. We examined aspects of collagen cross-linking in dystrophin-deficient murine, canine, and human skeletal muscle.
  
  
  
  DMD patient biopsies and samples from mdx mice and golden retriever muscular dystrophy dog samples (with appropriate controls) were analyzed. Collagen cross-linking was evaluated using solubility and hydroxyproline assays. Expression of the cross-linking enzyme lysyl oxidase (LOX) was determined by real-time polymerase chain reaction, immunoblotting, and immunofluorescence.
  
  
  
  LOX protein levels are increased in dystrophic muscle from all species evaluated. Dystrophic mice and dogs had significantly higher cross-linked collagen than controls, especially in the diaphragm. Distribution of intramuscular LOX was heterogeneous in all samples, but it increased in frequency and intensity in dystrophic muscle.
  
  
  
  These findings implicate elevated collagen cross-linking as an important component of the disrupted ECM in dystrophic muscles, and heightened cross-linking is evident in mouse, dog, and man. Muscle Nerve 54: 71-78, 2016.
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Smith
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, USA.|Myology Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Hammers
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, USA.|Myology Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.affiliation: Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Myology Institute, University of Florida, Gainesville, Florida, USA.|Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, 1864 Stadium Road, 124 Florida Gym, Gainesville, Florida, 32611, USA.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D003094:Collagen / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014746:Vimentin; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D006909:Hydroxyproline
keywords: collagen cross-linking; extracellular matrix; fibrosis; lysyl oxidase; muscular dystrophy