Satellite Cell

Point: Counter Point debate presentation on Satellite Cell function in Muscle Hypertrophy

1. SATELLITE CELL
ADDITION IS/IS NOT
OBLIGATORY FOR
SKELETAL MUSCLE
HYPERTROPHY

3. Nuclear Domain:
• Constant ratio
• Myonuclei/cell volume
HYPERTROPHY
At myofiber:
 Cross-sectional area
 Mass
 Protein content
 Cytoplasm volume
 Myonuclei #

4. Satellite cells:
• Progenitor cells
• Similar to stem cells
• Muscle precursor cells
• Location:
• Basal lamina
• Myofiber membrane
• Function:
• Muscle growth
• Muscle regeneration

6. During postnatal growth:
Satellite cell role Þ
• Myonuclear addition
• Myofiber formation

8. Synergist ablation
› surgical removal of
synergistic muscle
Testosterone
Clenbuterol
›β- Adrenergic agonist
Stretch Overload
Exercise
Satellite Cell
ACTIVATION
+
PROLIFERATION
Type I and Type II
Myofiber(s)
Ý TRANSCRIPTION
Ý TRANSLATION

?

9. Inhibition of myonuclear addition prevents
hypertrophy
Satellite cell ablation by local gamma irradiation
Assessing hypertrophy
›Muscle mass or myofiber cross-sectional area is
measured
Assessing satellite cell activity
›Enumeration, bromodeoxyuridine labeling, myoD
expression, and increases in myonuclear number

10. Lesions on satellite cells
Affects non-muscle cells that may prevent factors
that regulate satellite cell activity
Totally prevented local hypertrophy in adult rodents
after synergist ablation
Does not effect adaptive changes in myosin heavy
chain expression
Also, gamma irradiation used in the studies cited
does not meet levels commensurate with damage
and necrosis

11. Important: Multiple time points are necessary to
determine the roll of satellite cells!
›Many studies did not use later time points
“Myonuclear domain ceiling”
›Small increments may not change satellite cell #
›But additional increases may elicit satellite cell
proliferation

12. Satellite cell addition is NOT obligatory for
skeletal muscle hypertrophy (O’Connor &
Pavlath)
“Obligatory” =
›Mandatory, necessary, or essential
Provide evidence of skeletal muscle hypertrophy
in the absence of satellite cell addition

14. Investigated the effect of
1. Administered pharmacological agent
2. Contraction induced
3. Gamma irradiation
Induced skeletal muscle hypertrophy in the
absence of any increase in DNA content
OR increases in myonuclear number

15. Cimaterol/ clenbuterol
Administered via oral and intravenous
›Stimulates lipolysis
›Stimulates protein synthesis
›Stimulates blood flow
›Increases acute mobilization of nitrogen
›Increases amino acid uptake in the muscles

17. Conclusions
Examined:
›Whole body weight
›Muscle weight
›Fiber diameter
›Myonuclei number
Induced skeletal muscle hypertrophy without any
increase in satellite cells or increase in myonuclear
number
Increase in protein synthesis (RNA increase)

18. Sedentary Control No Reps
Mod Freq/Mod
Resistance
24 Reps, 500 gms
High Freq/ Low
Resistance
192 Reps, 0 gms
High Freq/ High
Resistance
192 Reps, 800-1100 gms
Wong & Booth, 1990

19. Results:
›Mod/Mod- No difference after acute exercise bouts
›High Freq/Low Resistance - Protein synthesis
increased 38%
›High Freq/High Resistance- No further increase in
protein synthesis over low resistance group
Wong & Booth, 1990

20. Exercise Protein
Synthesis
DNA Content Muscle
Hypertrophy
Concentric Increase Increase None
Eccentric Increase No IncreaseIncrease
Results:

22. Electrical stimulation alone did not cause muscle
hypertrophy
Combined with static stretch, protein synthesis
increased.
Increase rates of ribosomal capacities
Increase in RNA
No change in total DNA per muscle
Goldspink et al., 1995

25. Satellite cell addition does not occur as
measured by DNA content or nuclear number
Inhibition of satellite cell proliferation does not
inhibit skeletal muscle growth
Increase in hypertrophy due to increase in
protein synthesis

26. The following conditions need to be addressed:
›Analysis of time points (early and late) after
application of a hypertrophic stimulus
›Sufficiently large increases in myofiber cross-
sectional area or diameter
›Identify myonuclear number using a method to
clearly depict the sarcolemma
›To show cause and effect rather than correlation
after satellite cell removal

27. Various models of hypertrophy fail to satisfy one
or more of these criteria
›Do not provide conclusive evidence against the
necessity for satellite cells in hypertrophy
Satellite cell addition is obligatory, but set in
later stages due to a “myonuclear domain
ceiling”

28. Satellite cell and muscle regeneration well documented
Satellite cell role with hypertrophy debated
Timing of myonuclei addition unknown
Multiple time points required to determine satellite cell
role in hypertrophic model
Acute response:
›Enhanced transcription by myonuclei
Hypertrophic response may depend on the stimulus