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Muscle Nerve. 2016 Jun;54(1):71-8. doi: 10.1002/mus.24998. Epub 2016 Feb 22.

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

Smith LR1,2, Hammers DW1,2,3,4, Sweeney HL1,2,3,4, Barton ER2,4,5.

Author information

1
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2
Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3
Department of Pharmacology & Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, USA.
4
Myology Institute, University of Florida, Gainesville, Florida, USA.
5
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.

Abstract

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.

KEYWORDS:

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

PMID:
26616495
PMCID:
PMC5067682
DOI:
10.1002/mus.24998
[Indexed for MEDLINE]
Free PMC Article

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