背景:

前交叉韌帶撕裂導致股四頭肌萎縮，盡管進行了廣泛的康復治療，但仍難以恢復。最近的研究表明，損傷后股四頭肌的纖維負擔升高，這可能會限制恢復。闡明參與纖維化進展的機制和細胞類型對于開發(fā)新的治療策略至關(guān)重要。

目的:

確定導致?lián)p傷后纖維化負擔升高的因素。

研究設(shè)計:

描述性實驗室研究。方法:前交叉韌帶損傷后，從年輕成人(n = 14，平均±標準差:23±4年)受傷和未受傷的股外側(cè)肌中獲得肌肉活檢標本。測量肌肉生長抑制素、轉(zhuǎn)化生長因子β和其他調(diào)節(jié)因子的表達，并進行免疫組化分析以評估細胞外基質(zhì)成分的周轉(zhuǎn)。

結(jié)果:

損傷肢體骨骼肌肌生成抑制素基因(P <.005)和蛋白質(zhì)(P <.0005)表達，相關(guān)性(R2 = 0.38, P <.05)與成纖維細胞豐富。免疫組織化學分析顯示，人成纖維細胞表達激活素型IIB受體，分離的原代人肌肉源性成纖維細胞在體外肌生長抑制素處理后增殖增加(P <. 05)。肌肉細胞外基質(zhì)的主要成分膠原蛋白1和纖維連接蛋白在損傷肢體明顯升高(P <. 05)。在損傷肢體中，表達前膠原蛋白1的細胞豐度以及膠原蛋白重塑的新指標也有所升高(P <. 05)。

結(jié)論:

這些發(fā)現(xiàn)支持肌肉生長抑制素在ACL損傷后骨骼肌纖維性改變中的作用。

臨床相關(guān)性:

目前的研究表明，前交叉韌帶損傷后肌肉質(zhì)量下降的原因可能與肌生長抑制素表達升高有關(guān)，未來的研究應探索肌生長抑制素的治療抑制，以促進肌肉恢復和重返運動。

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.