Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.
Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.
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DOI：
10.1002/jor.23537
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Mendias CL
中科院分区：
文献类型：
--
作者：
Wurtzel CN;Gumucio JP;Grekin JA;Khouri RK Jr;Russell AJ;Bedi A;Mendias CL
前交叉韧带（ACL）撕裂是运动医学中最常见的膝关节损伤之一，美国每年的撕裂率高达25万。许多患有前交叉韧带撕裂的患者即使经过相当程度的康复也会持续萎缩和虚弱。肌生长抑制素是一种直接诱导肌肉萎缩的细胞因子，先前的研究表明，在前交叉韧带撕裂后，啮齿动物模型和患者的肌生长抑制素上调。使用临床前大鼠模型，我们的目的是确定使用对抗肌肉生长抑制素的生物中和抗体是否可以预防前交叉韧带撕裂后的肌肉萎缩和无力。大鼠接受手术诱导的前交叉韧带撕裂，并接受针对肌肉生长抑制素的生物中和抗体（10B3，葛兰素史克公司）或假抗体（E1-82.15，葛兰素史克公司）治疗。在诱导撕裂后7天或21天收获肌肉，以测量收缩功能、纤维大小和肌肉萎缩和肥大相关基因的变化。选择这些时间点来评估早期和后期肌肉结构和功能的变化。与假抗体组相比，前交叉韧带撕裂后7天，肌生长抑制素抑制降低了蛋白水解基因的表达，诱导了肥厚基因的表达。这些基因表达的早期变化导致前交叉韧带撕裂21天后肌纤维横截面积增加22%，最大等长力生产提高10%。总的来说，肌生长抑制素抑制导致了一些有利的，尽管适度的，肌肉再生的分子生物标志物的变化，减少了前交叉韧带撕裂后的肌肉萎缩和无力。
Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries in sports medicine, with tear rates in the US up to 250,000 per year. Many patients who suffer from ACL tears have persistent atrophy and weakness even after considerable rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies rodent models and patients have demonstrated an upregulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear. Rats underwent a surgically induced ACL tear and were treated with either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham antibody (E1-82.15, GlaxoSmithKline). Muscles were harvested at either 7 or 21 days after induction of a tear to measure changes in contractile function, fiber size and genes involved in muscle atrophy and hypertrophy. These time points were selected to evaluate early and later changes in muscle structure and function. Compared to the sham antibody group, seven days after ACL tear, myostatin inhibition reduced the expression of proteolytic genes and induced the expression of hypertrophy genes. These early changes in gene expression lead to a 22% increase in muscle fiber cross-sectional area and a 10% improvement in maximum isometric force production that were observed 21 days after ACL tear. Overall, myostatin inhibition lead to several favorable, although modest, changes in molecular biomarkers of muscle regeneration and reduced muscle atrophy and weakness following ACL tear.
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DOI：
10.1152/ajpregu.00121.2011
发表时间：
2011-09-01
影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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