Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice
Open accessAbstract
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: 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.
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In models of fully grown/developed mice (>4 months of age), short-term hypertrophy occurs in the absence of satellite cells.
“However, in models of fully grown/ developed mice (>4 months of age), short-term hypertrophy occurs in the absence of satellite cells [20,24,25].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [25]
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- Authors
- Murach, K. A., White, S. H., Wen, Y., Ho, A., Dupont-Versteegden, E. E., McCarthy, J. J., & Peterson, C. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Peterson, Charlotte A.
- Venue
- Skeletal Muscle
- Published
- 2017-07-10
- Volume
- 7
- Issue
- 1
- Pages
- 14-14
- ISSN
- 2044-5040 (ISSN-L)
- PMC
- PMC5504676
- OpenAlex
- W2736041272
- Cited by
- 156
- References
- 68
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 15 · 2023: 12 · 2022: 18 · 2021: 23 · 2020: 21 · 2019: 16 · 2018: 14 · 2017: 9
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Skeletal Muscle (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (F32AR071753, AR060701, AG049806)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- satellite cells, Pax7, muscle hypertrophy, myonuclear accretion, embryonic myosin heavy chain, muscle fiber cross-sectional area, muscle fiber number, developmental age, synergist ablation, plantaris muscle, postnatal muscle development
- MeSH terms
- Animals, Male, Mice, Inbred C57BL, Physical Conditioning, Animal, Muscle, Skeletal, Myosin Heavy Chains, Satellite Cells, Skeletal Muscle, Mice, PAX7 Transcription Factor
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