Department of Rehabilitation Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, Texas, USA.
Am J Sports Med. 2019 May;47(6):1385-1395. doi: 10.1177/0363546519832864. Epub 2019 Apr 17.
Anterior cruciate ligament (ACL) tears result in significant quadriceps muscle atrophy that is resistant to recovery despite extensive rehabilitation. Recent work suggests an elevated fibrotic burden in the quadriceps muscle after the injury, which may limit recovery. Elucidating the mechanisms and cell types involved in the progression of fibrosis is critical for developing new treatment strategies.
To identify factors contributing to the elevated fibrotic burden found after the injury.
Descriptive laboratory study.
After an ACL injury, muscle biopsy specimens were obtained from the injured and noninjured vastus lateralis of young adults (n = 14, mean ± SD: 23 ± 4 years). The expression of myostatin, transforming growth factor β, and other regulatory factors was measured, and immunohistochemical analyses were performed to assess turnover of extracellular matrix components.
Injured limb skeletal muscle demonstrated elevated myostatin gene ( P < .005) and protein ( P < .0005) expression, which correlated ( R = 0.38, P < .05) with fibroblast cell abundance. Immunohistochemical analysis showed that human fibroblasts express the activin type IIB receptor and that isolated primary human muscle-derived fibroblasts increased proliferation after myostatin treatment in vitro ( P < .05). Collagen 1 and fibronectin, primary components of the muscle extracellular matrix, were significantly higher in the injured limb ( P < .05). The abundance of procollagen 1-expressing cells as well as a novel index of collagen remodeling was also elevated in the injured limb ( P < .05).
These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury.
The current work shows that the cause of muscle quality decline after ACL injury likely involves elevated myostatin expression, and future studies should explore therapeutic inhibition of myostatin to facilitate improvements in muscle recovery and return to sport.
前交叉韧带（ACL）撕裂会导致显著的股四头肌萎缩，尽管进行了广泛的康复治疗，但这种萎缩仍难以恢复。最近的研究表明，ACL 损伤后股四头肌中的纤维化负担增加，这可能限制了恢复。阐明纤维化进展过程中的机制和细胞类型对于开发新的治疗策略至关重要。
确定导致 ACL 损伤后纤维化负担增加的因素。
描述性实验室研究。
在 ACL 损伤后，从年轻成年人（平均年龄±标准差：23±4 岁）的受伤和未受伤的股外侧肌中获取肌肉活检标本。测量肌肉生长抑制素、转化生长因子β和其他调节因子的表达，并进行免疫组织化学分析以评估细胞外基质成分的周转率。
受伤肢体骨骼肌表现出升高的肌肉生长抑制素基因（P<0.005）和蛋白表达（P<0.0005），与成纤维细胞数量呈正相关（R=0.38，P<0.05）。免疫组织化学分析表明，人成纤维细胞表达激活素 IIB 受体，并且分离的原代人肌肉来源成纤维细胞在体外接受肌肉生长抑制素处理后增殖增加（P<0.05）。受伤肢体的胶原 1 和纤维连接蛋白（肌肉细胞外基质的主要成分）明显升高（P<0.05）。受伤肢体的前胶原 1 表达细胞丰度以及胶原重塑的新指标也升高（P<0.05）。
这些发现支持在 ACL 损伤后，肌肉生长抑制素在促进骨骼肌的纤维生成改变中的作用。
目前的研究表明，ACL 损伤后肌肉质量下降的原因可能涉及肌肉生长抑制素的表达升高，未来的研究应探索肌肉生长抑制素的治疗抑制作用，以促进肌肉恢复和重返运动。
