Increased collagen cross-linking is a signature of dystrophin-deficient muscle

Lucas R. Smith, David W. Hammers, H. Lee Sweeney, Elisabeth R. Barton

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalMuscle and Nerve
Issue number1
StatePublished - Jul 1 2016
Externally publishedYes


  • collagen cross-linking
  • extracellular matrix
  • fibrosis
  • lysyl oxidase
  • muscular dystrophy

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)


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