Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

Kevin A. Murach, Sarah H. White, Yuan Wen, Angel Ho, Esther E. Dupont-Versteegden, John J. McCarthy, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Background: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Methods: Pax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Results: Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p < 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05), and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p < 0.05), and eMyHC expression was variable, specifically in mature SC+ mice. Conclusions: Reliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Original languageEnglish
Article number14
JournalSkeletal Muscle
Volume7
Issue number1
DOIs
StatePublished - Jul 10 2017

Bibliographical note

Funding Information:
This work was supported by grants from the NIH to KAM (AR071753), and to CAP and JJM (AG049806 and AR060701).

Publisher Copyright:
© 2017 The Author(s).

Keywords

  • Development
  • Fiber splitting
  • Muscle hypertrophy
  • Pax7
  • Regeneration
  • Synergist ablation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

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