Therapeutic Ultrasound Affects IGF-1 Splice Variant Expression in Human Skeletal Muscle

Abstract

Background: Animal models of skeletal muscle damage and repair demonstrate that therapeutic ultrasound (TUS) enhances muscle force recovery after damage, increases satellite cell proliferation, and decreases insulin-like growth factor (IGF)-1 splice variant (mechano growth factor) gene expression. However, these effects have not been verified in humans. Purpose: This study was undertaken to examine the 3 known splice variants of the IGF-1 gene in human skeletal muscle after damage and TUS treatment. Study Design: Controlled laboratory study. Methods: Sixteen healthy men (18-29 years of age), physically active, were randomized to either a control (CON) or experimental group (EXP). The EXP group underwent 200 lengthening contractions (muscle damage) of the quadriceps of both legs, 48 hours before TUS. Both groups received TUS, delivered for 10 minutes on a standardized area of the vastus lateralis of only 1 leg (1.0 MHz, 1.5 W/cm2). Bilateral muscle biopsy samples were taken from all participants, 6 hours after TUS. Total RNA was extracted, and quantitative real-time polymerase chain reaction conducted for each IGF-1 splice variant. Results: Muscle damage was confirmed by a decrease in the isometric peak torque and increase in creatine kinase activity levels 48 hours after damage (P < .01). After muscle damage, gene expression of total IGF-1 and 2 IGF-1 splice variants increased. Therapeutic ultrasound induced significant increase in IGF-1Eb gene expression in undamaged muscle (1.4 ± 0.2-fold, P < 0.01). In damaged skeletal muscle, no significant change in gene expression attributable to TUS was determined. Conclusion: Insulin-like growth factor–1 splice variants are differentially regulated in human skeletal muscle in response to exercise-induced muscle damage and TUS treatment. A single treatment of TUS in damaged muscle induces no change in the gene expression of the 3 IGF-1 splice variants in humans. In contrast, in undamaged skeletal muscle, TUS significantly increased IGF-1Eb splice variant gene expression. Clinical Relevance: These findings suggest that TUS may have additional therapeutic uses beyond its current common practice but may not be effective for muscle injury treatment in a young, healthy population.