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1Department of Orthopaedic Surgery, Growth and Development Laboratory, Children's Hospital of Pittsburgh and University of Pittsburgh, 2Department of Orthopaedic Surgery, Division of Sports Medicine, Musculoskeletal Research Center, University of Pittsburgh, 4Departments of Pharmacology and 5Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and 3Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan, Taiwan
Submitted 4 October 2002 ; accepted in final form 27 April 2003
Muscle injuries are very common in traumatology and sports medicine.
Although muscle tissue can regenerate postinjury, the healing process is slow
and often incomplete; complete recovery after skeletal muscle injury is
hindered by fibrosis. Our studies have shown that decreased fibrosis could
improve muscle healing. Suramin has been found to inhibit transforming growth
factor (TGF)-
1 expression by competitively binding to the
growth factor receptor. We conducted a series of tests to determine the
antifibrotic effects of suramin on muscle laceration injuries. Our results
demonstrate that suramin (50 µg/ml) can effectively decrease fibroblast
proliferation and fibrotic-protein expression (
-smooth muscle actin) in
vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine
muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle
regeneration, which led to efficient functional muscle recovery. These results
support our hypothesis that prevention of fibrosis could enhance muscle
regeneration, thereby facilitating more efficient muscle healing. This study
could significantly contribute to the development of strategies to promote
efficient muscle healing and functional recovery.
muscle injury; fibrosis; transforming growth factor-
1; suramin; muscle regeneration
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