背景:

前交叉韧带撕裂导致股四头肌萎缩，尽管进行了广泛的康复治疗，但仍难以恢复。最近的研究表明，损伤后股四头肌的纤维负担升高，这可能会限制恢复。阐明参与纤维化进展的机制和细胞类型对于开发新的治疗策略至关重要。

目的:

确定导致损伤后纤维化负担升高的因素。

研究设计:

描述性实验室研究。方法:前交叉韧带损伤后，从年轻成人(n = 14，平均±标准差:23±4年)受伤和未受伤的股外侧肌中获得肌肉活检标本。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，并进行免疫组化分析以评估细胞外基质成分的周转。

结果:

损伤肢体骨骼肌肌生成抑制素基因(P <.005)和蛋白质(P <.0005)表达，相关性(R2 = 0.38, P <.05)与成纤维细胞丰富。免疫组织化学分析显示，人成纤维细胞表达激活素型IIB受体，分离的原代人肌肉源性成纤维细胞在体外肌生长抑制素处理后增殖增加(P <. 05)。肌肉细胞外基质的主要成分胶原蛋白1和纤维连接蛋白在损伤肢体明显升高(P <. 05)。在损伤肢体中，表达前胶原蛋白1的细胞丰度以及胶原蛋白重塑的新指标也有所升高(P <. 05)。

结论:

这些发现支持肌肉生长抑制素在ACL损伤后骨骼肌纤维性改变中的作用。

临床相关性:

目前的研究表明，前交叉韧带损伤后肌肉质量下降的原因可能与肌生长抑制素表达升高有关，未来的研究应探索肌生长抑制素的治疗抑制，以促进肌肉恢复和重返运动。

Abstract

Background: 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.

Purpose: To identify factors contributing to the elevated fibrotic burden found after the injury.

Study design: Descriptive laboratory study.

Methods: 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.

Results: Injured limb skeletal muscle demonstrated elevated myostatin gene ( P < .005) and protein ( P < .0005) expression, which correlated ( R2 = 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).

Conclusion: These findings support a role for myostatin in promoting fibrogenic alterations within skeletal muscle after an ACL injury.

Clinical relevance: 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.

From:

Am J Sports Med. 2019 May;47(6):1385-1395.

 doi: 10.1177/0363546519832864. Epub 2019 Apr 17.