TY - JOUR
T1 - Mechanical Overloading Increases Maximal Force and Reduces Fragility in Hind Limb Skeletal Muscle from Mdx Mouse
AU - Ferry, Arnaud
AU - Parlakian, Ara
AU - Joanne, Pierre
AU - Fraysse, Bodvael
AU - Mgrditchian, Takouhie
AU - Roy, Pauline
AU - Furling, Denis
AU - Butler-Browne, Gillian
AU - Agbulut, Onnik
N1 - Funding Information:
Supported by Université Pierre et Marie Curie (A.F., D.F., G.B.B., O.A.), National Scientific Research Center–France (A.F., D.F., G.B., O.A.), INSERM (A.F., D.F., G.B.B.), University Paris Descartes (A.F.), and the Association Française contre les Myopathies grant number 16605 (A.F., D.F., G.B.B.).
Publisher Copyright:
© 2015 American Society for Investigative Pathology.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - There is fear that mechanical overloading (OVL; ie, high-force contractions) accelerates Duchenne muscular dystrophy. Herein, we determined whether short-term OVL combined with wheel running, short-term OVL combined with irradiation, and long-term OVL are detrimental for hind limb mdx mouse muscle, a murine model of Duchene muscular dystrophy exhibiting milder dystrophic features. OVL was induced by the surgical ablation of the synergic muscles of the plantaris muscle, a fast muscle susceptible to contraction-induced muscle damage in mdx mice. We found that short-term OVL combined with wheel and long-term OVL did not worsen the deficit in specific maximal force (ie, absolute maximal force normalized to muscle size) and histological markers of muscle damage (percentage of regenerating fibers and fibrosis) in mdx mice. Moreover, long-term OVL did not increase the alteration in calcium homeostasis and did not deplete muscle cell progenitors expressing Pax 7 in mdx mice. Irradiation before short-term OVL, which is believed to inhibit muscle regeneration, was not more detrimental to mdx than control mice. Interestingly, short-term OVL combined with wheel and long-term OVL markedly improved the susceptibility to contraction-induced damage, increased absolute maximal force, induced hypertrophy, and promoted a slower, more oxidative phenotype. Together, these findings indicate that OVL is beneficial to mdx muscle, and muscle regeneration does not mask the potentially detrimental effect of OVL.
AB - There is fear that mechanical overloading (OVL; ie, high-force contractions) accelerates Duchenne muscular dystrophy. Herein, we determined whether short-term OVL combined with wheel running, short-term OVL combined with irradiation, and long-term OVL are detrimental for hind limb mdx mouse muscle, a murine model of Duchene muscular dystrophy exhibiting milder dystrophic features. OVL was induced by the surgical ablation of the synergic muscles of the plantaris muscle, a fast muscle susceptible to contraction-induced muscle damage in mdx mice. We found that short-term OVL combined with wheel and long-term OVL did not worsen the deficit in specific maximal force (ie, absolute maximal force normalized to muscle size) and histological markers of muscle damage (percentage of regenerating fibers and fibrosis) in mdx mice. Moreover, long-term OVL did not increase the alteration in calcium homeostasis and did not deplete muscle cell progenitors expressing Pax 7 in mdx mice. Irradiation before short-term OVL, which is believed to inhibit muscle regeneration, was not more detrimental to mdx than control mice. Interestingly, short-term OVL combined with wheel and long-term OVL markedly improved the susceptibility to contraction-induced damage, increased absolute maximal force, induced hypertrophy, and promoted a slower, more oxidative phenotype. Together, these findings indicate that OVL is beneficial to mdx muscle, and muscle regeneration does not mask the potentially detrimental effect of OVL.
UR - http://www.scopus.com/inward/record.url?scp=84931381585&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/26009153
U2 - 10.1016/j.ajpath.2015.03.027
DO - 10.1016/j.ajpath.2015.03.027
M3 - Article
C2 - 26009153
AN - SCOPUS:84931381585
SN - 0002-9440
VL - 185
SP - 2012
EP - 2024
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 7
M1 - 2048
ER -