Therapeutic Myogenesis Induced by Ultrasound Exposure in a Volumetric Skeletal Muscle Loss Injury Model

Abstract

Background: Low-intensity pulsed ultrasound (LIPUS) irradiation has been shown to induce various responses in different cells. It has been shown that LIPUS activates extracellular signal–regulated kinase 1/2 (ERK1/2) through integrin. Purpose: To study the effects of LIPUS on myogenic regulatory factors and other related myogenesis elements in a volumetric skeletal muscle loss injury model. Study Design: Controlled laboratory study. Methods: C57BL/6J mice were subjected to full-thickness muscle defect injury of the quadriceps and treated with direct application of LIPUS 20 min/d or non-LIPUS treatment (control) for 3, 7, and 14 days. LIPUS was also applied to C2C12 cells in culture in the presence of low and high doses of lipopolysaccharides. The expression levels of myogenic regulatory factors and the expression levels of myokine-related and angiogenic-related proteins of the control and LIPUS groups were analyzed. Results: Muscle volume in the injury site was restored at day 14 with LIPUS treatment. Paired-box protein 7, myogenic factor 5, myogenin, and desmin expressions were significantly different between control and LIPUS groups at days 7 and 14. Myokine and angiogenic cytokine-related factors were significantly increased in the LIPUS group at day 3 and decreased with no significant difference between the groups by day 14. LIPUS induced different responses of myogenic regulatory factors in C2C12 cells with low and high doses of lipopolysaccharides. LIPUS promoted myogenesis through short-lived increase in interleukin-6 and heme oxygenase 1, together with activation of ERK1/2. Conclusion: LIPUS had a constant effect on the variables of tissue damage, from macrotrauma to microtrauma, leading to efficient muscle regeneration. Clinical Relevance: The focus of therapeutic strategies with LIPUS has been not only for microvascular regeneration but also for skeletal muscle and related local tissue recovery from acute or chronic damage.