title: Collagen crosslinking does not dictate stiffness in a transgenic mouse model of skeletal muscle fibrosis.
abstract: Skeletal muscle fibrosis is characterized by increases in tissue stiffness and collagen content. However, a very weak correlation exists between collagen content and stiffness in skeletal muscle. Recently, it has been hypothesized that collagen crosslinking explains tissue stiffness in fibrotic skeletal muscle. Therefore, we addressed this hypothesis by correlating tissue stiffness with lysyl-pyridinoline, hydroxylysyl-pyridinoline, and pentosidine collagen crosslinks. Stepwise regression revealed that, separate or together, collagen crosslinks did not correlate with tissue stiffness. Our result demonstrates that increased tissue stiffness in skeletal muscle fibrosis is not simply explained by increased collagen crosslinks and/or collagen crosslink density. We suggest that collagen organization may affect tissue stiffness.
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0863, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chapman
authors.affiliation: Department of Orthopaedic Surgery, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0863, USA.
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Pichika
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0863, USA; Department of Orthopaedic Surgery, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0863, USA; Department of Veteran׳s Affairs, 9500 Gilman Drive, La Jolla, CA, 92093-0863, USA. Electronic address: rlieber@ric.org.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005355:Fibrosis; D055595:Mechanical Phenomena; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D003432:Cross-Linking Reagents; D003094:Collagen
keywords: Collagen crosslinking; Extracellular matrix; Fibrosis; Mechanical properties; Muscle