Differential Requirement for Satellite Cells During Overload-Induced Muscle Hypertrophy in Growing Versus Mature Mice

Authors

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

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: Pax7^CreER-R26R^DTA 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.

Document Type

Article

Publication Date

7-10-2017

Notes/Citation Information

Published in Skeletal Muscle, v. 7, 14, p. 1-13.

© The Author(s). 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Digital Object Identifier (DOI)

https://doi.org/10.1186/s13395-017-0132-z

Funding Information

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

Related Content

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Repository Citation

Murach, Kevin A.; White, Sarah H.; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E.; McCarthy, John J.; and Peterson, Charlotte A., "Differential Requirement for Satellite Cells During Overload-Induced Muscle Hypertrophy in Growing Versus Mature Mice" (2017). Physical Therapy Faculty Publications. 79.
https://uknowledge.uky.edu/rehabsci_facpub/79