Abstract #T63

# T63
­Interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 and fibroblast growth factor-2 alter proliferation and differentiation of equine satellite cells.
Emma K. LaVigne*1, Alfredo Sanchez Londoño2, Sarah A. Reed1, 1Department of Animal Science, University of Connecticut, Storrs, CT, 2Department of Environmental and Population Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA.

Muscle growth in young horses occurs by hypertrophy of individual muscle fibers, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells are muscle stem cells that reside between the sarcolemma and the basal lamina of the muscle fiber and can be stimulated or inhibited in response to different cytokines and growth factors. We hypothesized that interleukin (IL)-6, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1 and fibroblast growth factor (FGF)-2 would alter proliferation and differentiation in satellite cells isolated from young horses. Satellite cells obtained from 10 d old foals (n = 4) were cultured individually in the presence of 10 ng/mL IL-6, 20 ng/mL TNF-α, 25 ng/mL IGF-1 or 10 ng/mL FGF-2 to determine the effects on proliferation and differentiation (3 wells per treatment group per horse). Proliferation was measured by incorporation of 5-ethynyl-2'-deoxyuridine (EdU) into cells in S phase. Differentiation was measured by quantifying the fusion index (the number of nuclei present in multinucleated myofibers divided by the total number of nuclei). Data were analyzed using the MIXED procedure in SAS; P < 0.05 was considered significant. Interleukin-6 and TNF-α decreased satellite cell proliferation compared with control cells (14.9% and 11.5%, respectively; P ≤ 0.01). Fusion into myotubes was increased 6.2% in the presence of IL-6 (P = 0.001) but decreased 8.7% by TNF-α (P < 0.0001). Satellite cell proliferation was increased 28.8% in the presence of IGF-1 (P < 0.0001) and 73.0% in the presence of FGF-2 (P < 0.0001) compared with controls. Insulin-like growth factor-1 increased fusion 3.5% (P = 0.0087) and FGF-2 decreased fusion 13.1% (P < 0.0001). By differentially stimulating or inhibiting proliferation and fusion of satellite cells, IL-6, TNF-α, IGF-1 and FGF-2 significantly affect muscle hypertrophy. Dysregulation of these cytokines or growth factors, therefore, can lead to detrimental muscle degradation, inflammation, and impaired growth.

Key Words: satellite cells, horse, inflammation