Aging Aggravates the Progression of Muscle Degeneration After Rotator Cuff Tears in Mice
Aging Aggravates the Progression of Muscle Degeneration After Rotator Cuff Tears in Mice
复制标题
衰老会加剧小鼠肩袖撕裂后肌肉退化的进展
DOI：
10.1016/j.arthro.2021.09.014
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Horiuchi Keisuke
中科院分区：
文献类型：
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作者：
Takada Yuhei;Matsumura Noboru;Shirasawa Hideyuki;Yoda Masaki;Matsumoto Morio;Nakamura Masaya;Horiuchi Keisuke
目的探讨衰老对小鼠肩袖撕裂（RCT）后肌肉变性的影响。方法选用幼年（12周龄）和老年（50 ~ 60周龄）雌性C57BL/6小鼠，每组29只。切除肩袖，切除肱骨近端以诱导肩袖肌肉退行性变。这些小鼠在手术后4周和12周被安乐死（分别称为rct -4周小鼠和rct -12周小鼠），并与假药小鼠进行比较。收集冈上肌进行组织学、Western blot分析和基因表达分析。结果老龄RCT-4wk小鼠和老龄RCT-12wk小鼠的脂肪组织均较假药老龄小鼠显著增加（P= .001），脂肪面积比显著高于老龄RCT-4wk小鼠（P< .001）。老龄RCT-4wk小鼠（P= 0.002）和老龄RCT-12wk小鼠（P< 0.001）的脂肪面积均明显大于相应的幼龄小鼠。老年rct -12周小鼠的肌肉纤维化与老年假药治疗小鼠（P= 0.005）和年轻rct -12周小鼠（P= 0.016）相比显著增加。与年轻RCT小鼠相比，老年RCT小鼠的perilipin的表达以及脂肪生成和纤维化分化标记物的转录物也显著增加。结论衰老在RCT后肌肉脂肪浸润和纤维化的病理过程中起关键作用，且随着时间的推移，老年小鼠的肌肉退行性变发生。在小鼠RCT模型中，衰老促进肌肉退化的进展。此外，本研究表明，即使没有去神经支配，老年小鼠也会发生肌肉退行性变，本研究所描述的模型是研究肌肉退行性变病理的有用工具。
PurposeThe purpose of this study was to evaluate the impact of aging on muscle degeneration after rotator cuff tear (RCT) in mice.MethodsYoung (12-week-old) and aged (50-to-60-week-old) female C57BL/6 mice were used (n= 29 for each group). The rotator cuff was transected, and the proximal humerus was removed to induce degeneration of the rotator cuff muscles. The mice were euthanized 4 and 12 weeks after the procedure (referred to as RCT-4wk mice and RCT-12wk mice, respectively) and compared with the sham-treated mice. The supraspinatus muscles were collected for histology, Western blot analysis, and gene expression analyses.ResultsThere was a significant increase in fat tissue in aged RCT-4wk mice (P= .001) and aged RCT-12wk mice (P< .001) compared with sham-treated aged mice, and aged RCT-12wk mice had a significantly increased fat area ratio compared with aged RCT-4wk mice (P< .001). The fat area was significantly larger in both the aged RCT-4wk (P= .002) and RCT-12wk mice (P< .001) than in the corresponding young mice. Muscular fibrosis was significantly increased in aged RCT-12wk mice compared with aged sham-treated mice (P= .005) and young RCT-12wk mice (P= .016). There were also significant increases in the expression of perilipin and transcripts of adipogenic and fibrogenic differentiation markers in aged RCT mice compared with young RCT mice.ConclusionThe present results show that aging is critically involved in the pathology of muscular fatty infiltration and fibrosis after RCT, and muscular degeneration progresses over time in aged mice.Clinical RelevanceAging promotes the progression of muscle degeneration in a mouse RCT model. Furthermore, this study shows that muscle degeneration occurs in aged mice even without denervation and that the model described in the present study is a useful tool for studying the pathology of muscle degeneration.