Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
Open accessAbstract
An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.
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Satellite cell-depleted muscles show a normal hypertrophic response to overload in the short term.
“In contrast, satellite cell-depleted muscles show a normal hypertrophic response to overload in the short term (93).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [93]
Muscular stem cells, also called satellite cells, play an important role in sarcopenia; they are responsible for skeletal muscle repair following damage and play an important role in the maintenance of muscle mass with advancing age.
“muscular stem cells, also called “satellite cells,” play an important role. They are responsible for skeletal muscle repair following damage [24] and have been implicated in regulating extracellular matrix production during hypertrophy and regenerative processes, and therefore play an important role in the maintenance of muscle mass with advancing age [25,26].”
From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [24]
Satellite cells are primarily responsible for driving skeletal muscle repair in response to damaging stimuli such as exercise contraction.
“Muscle stem cells commonly known as satellite cells, are primarily responsible for driving the skeletal muscle repair process to potentially damaging stimuli, such as mechanical stress elicited by exercise contraction.”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [20]
Upon activation, satellite cells enter the cell cycle, proliferate, differentiate to myoblasts and myocytes in myogenesis, and fuse to damaged muscle fibers.
“Upon their activation, satellite cells enter the cell cycle, proliferate, differentiate to myoblasts and myocytes in a process termed myogenesis, and fuse to damaged muscle fibers.”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [20]
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 [20]
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- Authors
- McCarthy, J. J., Mula, J., Miyazaki, M., Erfani, R., Garrison, K., Farooqui, A. B., Srikuea, R., Lawson, B. A., Grimes, B., Keller, C., Van Zant, G., Campbell, K. S., Esser, K. A., Dupont-Versteegden, E. E., & Peterson, C. A.
- Affiliations
- University of Kentucky (US)
- Oregon Health & Science University (US)
- Division of Hematology and Oncology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
- Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA.
- Corresponding author
- Peterson, Charlotte A.
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2011-09-01
- Volume
- 138
- Issue
- 17
- Pages
- 3657-3666
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC3152923
- OpenAlex
- W2132035753
- Cited by
- 616
- References
- 57
- Citations by year
- 2026: 19 · 2025: 18 · 2024: 25 · 2023: 38 · 2022: 35 · 2021: 48 · 2020: 58 · 2019: 44 · 2018: 41 · 2017: 42 · 2016: 50 · 2015: 52 · 2014: 46 · 2013: 50 · 2012: 46
- FWCI
- 18.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG020941, R21AG034453, AG034453, R01AG020941)
- National Heart, Lung, and Blood Institute (R01HL090749, HL090749)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR045617, R01AR060701, AR060701, R01AR045617)
- 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 › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- satellite cells, skeletal muscle hypertrophy, tamoxifen, mechanical overload, myonuclear domain, muscle regeneration, specific force, calcium sensitivity, cross-bridge cycling, muscle plasticity
- MeSH terms
- Animals, Female, Flow Cytometry, Hypertrophy, Tamoxifen, Blotting, Western, Polymerase Chain Reaction, Muscle, Skeletal, Muscle Fibers, Skeletal, Satellite Cells, Skeletal Muscle, Mice
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