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

Nuclear Domain:• Constant ratio• Myonuclei/cell volume

HYPERTROPHYAt myofiber: Cross-sectional area Mass Protein content Cytoplasm volume Myonuclei #

Satellite cells: • Progenitor cells

• Similar to stem cells• Muscle precursor cells

• Location:• Basal lamina • Myofiber membrane

• Function:• Muscle growth• Muscle regeneration

During postnatal growth:Satellite cell role • Myonuclear addition• Myofiber formation

Synergist ablation› surgical removal of

synergistic muscle Testosterone Clenbuterol

› β- Adrenergic agonist Stretch Overload Exercise

Satellite CellACTIVATION

+PROLIFERATION

Type I and Type IIMyofiber(s)

TRANSCRIPTION TRANSLATION

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

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

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

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

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

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

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)

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

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 groupWong & Booth, 1990

Exercise Protein Synthesis

DNA Content Muscle Hypertrophy

Concentric Increase Increase None

Eccentric Increase No Increase Increase

Results:

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

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

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

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”

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