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Satellite Cell‐Mediated Myonuclear Accretion Is Required For Mechanical Overload‐Induced Hypertrophy In Young Growing Mice
Author(s) -
Murach Kevin,
White Sarah,
Wen Yuan,
Ho Angel,
Kosmac Kate,
McCarthy John,
Peterson Charlotte
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.713.10
Subject(s) - muscle hypertrophy , plantaris muscle , myosin , medicine , endocrinology , satellite , tamoxifen , skeletal muscle , cell growth , biology , cell , immunohistochemistry , anatomy , chemistry , microbiology and biotechnology , soleus muscle , physics , genetics , astronomy , cancer , breast cancer
When skeletal muscle hypertrophy is induced by mechanical or genetic means, numerous investigations report that satellite cell‐mediated myonuclear accretion is not required to promote muscle growth in adult mice (≥16 weeks old). However, recent evidence suggests that the satellite cell requirement during hypertrophy is influenced by maturational age. That is, if a hypertrophic stimulus is imposed on growing muscle during adolescence, satellite cell‐mediated myonuclear accretion may become necessary to support the additional growth. The purpose of this investigation was to rigorously test whether maturational age alters the requirement for satellite cell‐mediated myonuclear accretion during mechanically‐induced skeletal muscle hypertrophy. Using the Pax7 CreR ‐R26R DTA mouse, we conditionally depleted satellite cells in adolescent mice (8 weeks of age) via five consecutive daily tamoxifen injections, then allowed a two‐week washout (SC−). Age‐matched vehicle‐treated Pax7 CreR ‐R26R DTA mice were used as controls (SC+). Tamoxifen‐ and vehicle‐treated mice were then sham surgerized or synergist ablated for 10 days via a modified technique that overloads the plantaris muscle but minimizes muscle regeneration (n=6–8 per group). Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area were evaluated via immunohistochemistry. Myonuclear counts (myonuclei/100 millimeters) were performed on isolated single muscle fibers. Only tamoxifen‐treated mice with ≥90% satellite cell depletion were included in this analysis. Following 10 days of mechanical overload of the plantaris, SC+ mice experienced a 60% increase in satellite cell density (P<0.05). Muscle fiber cross sectional area and myonuclear number increased by 20% in SC+ (P<0.05), but did not change in SC− mice (P>0.05). Expression of eMyHC across all mice was <2%, indicating that overload surgery did not induce a regenerative response. Resident myonuclei of young growing mice appear inherently different than those of adult mice in their ability to compensate during hypertrophy without satellite cells. Support or Funding Information NIH RO1 AR060701 07