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From the Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
* Address correspondence to Johnny Huard, PhD, University of Pittsburgh, Department of Orthopaedic Surgery, Children’s Hospital of Pittsburgh, 3460 Fifth Avenue, 4100 Rangos Research Center, Pittsburgh, PA 15213 (e-mail: jhuard{at}pitt.edu).
Background: Muscle strain injuries are extremely common in sports medicine. Muscle healing often is hindered by scar tissue formation after injury.
Hypothesis: Suramin can prevent scar tissue formation and improve muscle healing after injury because of its ability to antagonize transforming growth factor–ß1, a fibrotic cytokine.
Study Design: Controlled laboratory study.
Materials and Methods: In vitro, muscle-derived fibroblasts (a potential cell source of muscle fibrosis) were incubated with suramin and/or transforming growth factor–ß1; a cell growth curve was obtained. In vivo, mouse gastrocnemius muscles were strain injured. Suramin or sham/control intramuscular injections were performed after injury at various time points. Mice were sacrificed at various time points after injury, and skeletal muscle tissue was evaluated by using histological and physiological tests. Statistical analysis was performed by using analysis of variance and Fisher tests.
Results: Suramin decreased the stimulating effect of transforming growth factor–ß1 on the growth of muscle-derived fibroblasts in vitro. Significantly less fibrous scar formation was observed in suramin-treated muscles than in sham-injected muscles. The fast-twitch and tetanus strength of suramin-treated muscles was also significantly greater relative to that of control muscles.
Conclusions: Suramin blocked the stimulatory effect of transforming growth factor–ß1 on muscle-derived fibroblasts in vitro. Suramin also reduced fibrous scar formation in muscle and enhanced muscle strength in strain-injured skeletal muscle.
Clinical Relevance: These results may facilitate the development of strategies to enhance muscle healing after injury.
Key Words: suramin • antifibrosis • muscle strain injury • muscle healing
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