The initial delay to mitotic activity in primary cultures of equine satellite cells is reduced by combinations of growth factors.
Abstract: Satellite cell (SC) activation is defined as the time frame during which the stem cell becomes poised to reenter G1 of the cell cycle. The growth factors and events leading to full mitotic activation in equine SCs remain largely unknown. Insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), and fibroblast growth factor 2 (FGF2) are sequentially transcribed during the muscle repair and recovery period following strenuous exercise in adult horses. Expression of IGF-I occurs within 24 h of the postexercise recovery period suggesting it may affect early SC actions. As a first step, gluteus medius muscle cryosections from adult horses (n = 9) were examined for the presence of central nuclei (CN), a marker of SC addition to the fiber. Results demonstrate few CN fibers prior to exercise with a 3-fold increase (P = 0.05) 24 h postexercise. Cultures of SC (n = 4 isolates) were treated with 100 ng/mL IGF-I for varying times prior to measurement of myogenic events. Results demonstrate that IGF-I does not affect the initial lag period, proliferation, or subsequent differentiation of equine SC in vitro (P > 0.05). However, media containing a combination of IGF-I and 10 ng/mL FGF2 and 25 ng/mL HGF hastens (P < 0.05) the time to S-phase entry in fresh isolates of SCs. Media supplementation with optimal concentrations of FGF2, HGF, or a combination of HGF and FGF2 suppresses (P < 0.05) the percentage of myogenin immunopositive SCs to levels below that found in control- or IGF-I-treated SCs. These results provide new insight into the combinatorial roles growth factors play during equine SC myogenesis. Satellite cells are the resident stem cells found within skeletal muscle. Following strenuous exercise, the cells become mitotically active to supply progenitors for muscle repair. The signals responsible for their exit from the dormant state are largely unknown. Hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor I (IGF-I) are located within the local environment postexercise suggesting their involvement in mitotic activation. Treatment of satellite cells in vitro with optimal concentrations of HGF, FGF2, or IGF-I did not affect transition into the cell cycle. By contrast, inclusion of all three growth factors in the media caused an increase in the numbers of activated satellite cells. The combination of factors suppressed expression of myogenin, the requisite transcriptional mediator of differentiation. Although IGF-I stimulates myogenin expression in other muscle cell types, a similar response was not observed in equine satellite cells. These results support a role for HGF, FGF2, and IGF-I during the initial postexercise repair period in horses.
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Publication Date: 2022-08-01 PubMed ID: 35908788PubMed Central: PMC9339324DOI: 10.1093/jas/skac140Google Scholar: Lookup
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Summary
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The research investigates the effects of various growth factors on the activation and differentiation of horse muscle stem cells, known as satellite cells (SC), after exercise. The study revealed that a combination of insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), and fibroblast growth factor 2 (FGF2) enhanced the reentry of stem cells into the cell cycle, promoting muscle repair.
Study rationale and objectives
- The study was instigated to identify the growth factors and the sequence of events leading to the full activation and function of equine satellite cells (the resident stem cells found within skeletal muscle).
- This was considered important as satellite cells play critical roles in muscle repair following strenuous exercise, but the signals responsible for their activation aren’t clearly understood.
Methodology
- The researchers examined gluteus medius muscle sections from adult horses after exercise.
- The presence of central nuclei, an indicator of satellite cell addition to the muscle fiber, was assessed.
- Isolated satellite cells were treated with varying concentrations of IGF-I and other combinations of growth factors and their impact on the cell cycle and myogenic (muscle-forming) events were measured.
Findings
- A significant increase in central nuclei was observed in the muscle fibers following exercise, indicating satellite cell activation.
- When treated alone, IGF-I did not make any significant impact on the processes of satellite cell activation or differentiation.
- However, a combination of growth factors (IGF-I, HGF, and FGF2) was found to hasten the reentry of satellite cells into the cell cycle (S-phase entry), implying a faster and more effective activation and potential muscle repair process.
- Moreover, when the satellite cells were supplemented with HGF, FGF2, or both, a suppression of myogenin (an essential protein for muscle differentiation) expression was observed, signifying some delay or control over the differentiation of satellite cells.
Conclusion
- The study provides valuable insights into the roles and interactions of various growth factors in the processes of satellite cell activation and muscle repair post-exercise.
- The findings also suggest that a combination of growth factors (HGF, FGF2, and IGF-I) might be crucial during the initial stages of muscle repair after exercise in horses.
Cite This Article
APA
Barshick MR, Gonzalez ML, Busse NI, Helsel PJ, Johnson SE.
(2022).
The initial delay to mitotic activity in primary cultures of equine satellite cells is reduced by combinations of growth factors.
J Anim Sci, 100(8), skac140.
https://doi.org/10.1093/jas/skac140 Publication
Researcher Affiliations
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
MeSH Terms
- Animals
- Cells, Cultured
- Fibroblast Growth Factor 2 / metabolism
- Fibroblast Growth Factor 2 / pharmacology
- Horses
- Insulin-Like Growth Factor I / metabolism
- Muscle Development
- Muscle, Skeletal / metabolism
- Myoblasts
- Satellite Cells, Skeletal Muscle / metabolism
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