Improved muscle healing after contusion injury by the inhibitory effect of suramin on myostatin, a negative regulator of muscle growth.
BACKGROUND
Muscle contusions are the most common muscle injuries in sports medicine. Although these injuries are capable of healing, incomplete functional recovery often occurs.


OBJECTIVE
Suramin enhances muscle healing by both stimulating muscle regeneration and preventing fibrosis in contused skeletal muscle.


METHODS
Controlled laboratory study.


METHODS
In vitro: Myoblasts (C2C12 cells) and muscle-derived stem cells (MDSCs) were cultured with suramin, and the potential of suramin to induce their differentiation was evaluated. Furthermore, MDSCs were cocultured with suramin and myostatin (MSTN) to monitor the capability of suramin to neutralize the effect of MSTN. In vivo: Varying concentrations of suramin were injected in the tibialis anterior muscle of mice 2 weeks after muscle contusion injury. Muscle regeneration and scar tissue formation were evaluated by histologic analysis and functional recovery was measured by physiologic testing


RESULTS
In vitro: Suramin stimulated the differentiation of myoblasts and MDSCs in a dose-dependent manner. Moreover, suramin neutralized the inhibitory effect of MSTN on MDSC differentiation. In vivo: Suramin treatment significantly promoted muscle regeneration, decreased fibrosis formation, reduced myostatin expression in injured muscle, and increased muscle strength after contusion injury.


CONCLUSIONS
Intramuscular injection of suramin after a contusion injury improved overall skeletal muscle healing. Suramin enhanced myoblast and MDSC differentiation and neutralized MSTN's negative effect on myogenic differentiation in vitro, which suggests a possible mechanism for the beneficial effects that this pharmacologic agent exhibits in vivo.


CONCLUSIONS
These findings could contribute to the development of biological treatments to aid in muscle healing after experiencing a muscle injury.
Nozaki
Masahiro
M
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh,Pennsylvania, USA.
Li
Yong
Y
Zhu
Jinhong
J
Ambrosio
Fabrisia
F
Uehara
Kenji
K
Fu
Freddie H
FH
Huard
Johnny
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003288:Contusions / Q000188:drug therapy*; D015536:Down-Regulation; D005355:Fibrosis / Q000188:drug therapy; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects*; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D000970:Antineoplastic Agents; D055435:Myostatin; D013498:Suramin