Improved Muscle Healing After Contusion Injury by the Inhibitory Effect of Suramin on Myostatin, a Negative Regulator of Muscle Growth
Improved Muscle Healing After Contusion Injury by the Inhibitory Effect of Suramin on Myostatin, a Negative Regulator of Muscle Growth
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DOI：
10.1177/0363546508322886
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发表时间：
2008-12-01
影响因子：
4.8
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Nozaki, Masahiro;Li, Yong;Huard, Johnny
背景：肌肉挫伤是运动医学中最常见的肌肉损伤。假设：苏拉明通过刺激肌肉再生和防止挫伤骨骼肌纤维化来增强肌肉愈合。研究设计：对照实验室研究。方法：体外：将成肌细胞（C2C12细胞）和肌源性干细胞（MDSC）与苏拉明一起培养，并评估苏拉明诱导其分化的潜力。此外，MDSC与苏拉明和肌肉生长抑制素（MSTs）共培养以监测苏拉明中和MSTs的作用的能力。体内：在肌肉挫伤后2周，在小鼠胫骨前肌中注射不同浓度的苏拉明。结果：体外实验：苏拉明以剂量依赖性方式刺激成肌细胞和MDSCs的分化，并与成肌细胞和MDSCs的分化率呈显著正相关。此外，苏拉明中和了Mesenchase对MDSC分化的抑制作用。体内：苏拉明治疗显着促进肌肉再生，减少纤维化形成，减少肌肉生长抑制素在受伤的肌肉表达，并增加肌肉力量后挫伤injure.Conclusion：苏拉明肌肉注射后，挫伤改善整体骨骼肌愈合。苏拉明增强成肌细胞和MDSC的分化和中和Mesozoic的负面影响，在体外的成肌分化，这表明一个可能的机制，这种药理学代理表现出在vivo.Clinical Relevance的有益效果：这些发现可能有助于生物治疗的发展，以帮助肌肉愈合后，经历了肌肉损伤。
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 testingResults: 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.