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Published on: September 18, 2019
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
John J McCarthy1, Jyothi Mula, Mitsunori Miyazaki
1Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Abstract:
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, Ca(2+) 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.
Insights
Satellite cells are not essential for skeletal muscle hypertrophy in adult mice. Muscle fibers can significantly increase in size and mass following mechanical overload without satellite cell support.
Area of Science:
- Skeletal Muscle Physiology
- Cellular Biology
- Muscle Plasticity
Background:
- The role of satellite cells in skeletal muscle hypertrophy remains an important unresolved question.
- Satellite cells are critical for muscle regeneration and repair.
Purpose of the Study:
- To investigate whether satellite cells are necessary for muscle fiber hypertrophy in mature skeletal muscle.
- To test the hypothesis that satellite cells are required for skeletal muscle to increase in mass and size under mechanical overload.
Main Methods:
- A novel Pax7-DTA mouse model was used for conditional ablation of satellite cells (>90%) in mature skeletal muscle.
- Mechanical overload was induced in the plantaris muscle via synergist ablation in adult mice.
- Muscle mass, fiber cross-sectional area, myonuclear content, and single-fiber function were analyzed after two weeks of overload.
Main Results:
- Satellite cell-depleted muscles exhibited robust hypertrophy, with approximately twofold increases in muscle mass and fiber size, comparable to control groups.
- Despite hypertrophy, satellite cell-depleted fibers lacked the typical increase in myonuclei, leading to expanded myonuclear domains.
- No significant differences in specific force or other functional parameters were observed between hypertrophied fibers with or without satellite cells.
- Fiber hyperplasia and regeneration were significantly reduced in the absence of satellite cells.
Conclusions:
- Skeletal muscle fibers can achieve significant hypertrophy in response to mechanical overload independently of satellite cells.
- Satellite cells play a distinct role in processes like fiber hyperplasia and regeneration, but not in the primary hypertrophic response of existing fibers.
- These findings challenge the necessity of satellite cells for muscle mass increase in mature skeletal muscle under overload conditions.
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