title: The passive mechanical properties of the extensor digitorum longus muscle are compromised in 2- to 20-mo-old mdx mice.
abstract: Muscle rigidity and myotendinous junction (MTJ) deficiency contribute to immobilization in Duchenne muscular dystrophy (DMD), a lethal disease caused by the absence of dystrophin. However, little is known about the muscle passive properties and MTJ strength in a diseased muscle. Here, we hypothesize that dystrophin-deficient muscle pathology renders skeletal muscle stiffer and MTJ weaker. To test our hypothesis, we examined the passive properties of an intact noncontracting muscle-tendon unit in mdx mice, a mouse model for DMD. The extensor digitorum longus (EDL) muscle-tendon preparations of 2-, 6-, 14-, and 20-mo-old mdx and normal control mice were strained stepwisely from 110% to 160% of the muscle optimal length. The stress-strain response and failure position were analyzed. In support of our hypothesis, the mdx EDL preparation consistently developed higher stress before muscle failure. Postfailure stresses decreased dramatically in mdx but not normal preparations. Further, mdx showed a significantly faster stress relaxation rate. Consistent with stress-strain assay results, we observed significantly higher fibrosis in mdx muscle. In 2- and 6-mo-old mdx and 20-mo-old BL10 mice failure occurred within the muscle (2- to 14-mo-old BL10 preparations did not fail). Interestingly, in ≥14-mo-old mdx mice the failure site shifted toward the MTJ. Electron microscopy revealed substantial MTJ degeneration in aged but not young mdx mice. In summary, our results suggest that the passive properties of the EDL muscle and the strength of MTJ are compromised in mdx in an age-dependent manner. These findings offer new insights in studying DMD pathogenesis and developing novel therapies.
authors.affiliation: Dept. of Molecular Microbiology and Immunology, Univ. of Missouri, One Hospital Dr., Columbia, MO 65212, USA. duand@missouri.edu
authors.forename: Chady H
authors.initials: CH
authors.lastname: Hakim
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grange
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Duan
mesh_terms: D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D004195:Disease Models, Animal; D004548:Elasticity; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D046529:Microscopy, Electron, Transmission; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013314:Stress, Mechanical; D013710:Tendons / Q000503:physiopathology; D014783:Viscosity
chemical_list: D006909:Hydroxyproline