Improved muscle healing after contusion injury by the inhibitory effect of suramin on myostatin, a negative regulator of muscle growth

Nozaki, M and Yong, Li and Jinhong, Zhu and Ambrosio, F and Uehara, K and Fu, FH and Huard, J (2008) Improved muscle healing after contusion injury by the inhibitory effect of suramin on myostatin, a negative regulator of muscle growth. American Journal of Sports Medicine, 36 (12). 2354 - 2362. ISSN 0363-5465

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Abstract

Background: Muscle contusions are the most common muscle injuries in sports medicine. Although these injuries are capable of healing, incomplete functional recovery often occurs. Hypothesis: Suramin enhances muscle healing by both stimulating muscle regeneration and preventing fibrosis in contused skeletal muscle. Study Design: 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. Conclusion: 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. Clinical Relevance: These findings could contribute to the development of biological treatments to aid in muscle healing after experiencing a muscle injury. © 2008 American Orthopaedic Society for Sports Medicine.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Nozaki, M Yong, Li Jinhong, Zhu Ambrosio, F faa7@pitt.edu FAA7 Uehara, K Fu, FH ffu@pitt.edu FFU Huard, J
Centers:	Other Centers, Institutes, or Units > Stem Cell Research Center
Date:	1 December 2008
Date Type:	Publication
Journal or Publication Title:	American Journal of Sports Medicine
Volume:	36
Number:	12
Page Range:	2354 - 2362
DOI or Unique Handle:	10.1177/0363546508322886
Schools and Programs:	School of Medicine > Orthopaedic Surgery School of Medicine > Physical Medicine and Rehabilitation Swanson School of Engineering > Bioengineering
Refereed:	Yes
ISSN:	0363-5465
MeSH Headings:	Animals; Antineoplastic Agents--pharmacology; Antineoplastic Agents--therapeutic use; Cell Differentiation--drug effects; Cell Line; Contusions--drug therapy; Down-Regulation; Fibrosis--drug therapy; Injections, Intramuscular; Male; Mice; Mice, Inbred C57BL; Muscle Strength--drug effects; Muscle, Skeletal--drug effects; Muscle, Skeletal--injuries; Muscle, Skeletal--pathology; Myoblasts--drug effects; Myostatin--antagonists & inhibitors; Myostatin--metabolism; Regeneration--drug effects; Stem Cells--drug effects; Suramin--pharmacology; Suramin--therapeutic use; Wound Healing--drug effects
PubMed ID:	18725651
Date Deposited:	15 May 2014 20:26
Last Modified:	03 Feb 2019 04:55
URI:	http://d-scholarship.pitt.edu/id/eprint/21601

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