Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice
Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice
复制标题
DOI：
10.1186/2044-5040-4-10
复制
发表时间：
2014-05-23
期刊：
影响因子：
4.9
通讯作者：
Banks, Glen B.
中科院分区：
文献类型：
--
作者：
Faber, Rachel M.;Hall, John K.;Banks, Glen B.
背景资料：杜氏肌营养不良症（DMD）mdx小鼠模型中的肌肉肥大可以通过维持峰值力产生来部分补偿肌营养不良蛋白的损失。肥大肌肉的组织学检查表明，肥大主要是由于肌纤维的增加，并伴有运动轴突分支。然而，尚不清楚神经支配的肌纤维数量的增加是否（肌纤维增生）导致mdx小鼠的肌肉肥大。为了更好地理解mdx小鼠肌肉肥大的细胞机制，我们直接比较了趾长伸肌（EDL）肌肉中营养不良病理学的时间进展与肌纤维数量、肌纤维分支和神经支配，从3到20周龄。结果：我们发现，28%的增加，在横截面的肌肉纤维的数量与31%的增加，肌纤维分支。值得注意的是，肌纤维数量和肌纤维分支的最大增加发生在12周龄后，此时具有中央核的肌纤维的比例已经稳定并且mdx小鼠已经达到成熟。营养不良的病理学与肌肉神经支配的深刻变化相一致，包括坏死纤维的暂时去神经支配、突触碎片和超末端轴突发芽。然而，在3到20周龄的mdx小鼠中几乎没有突触形成的证据。只有4.4%的神经肌肉接头延长超终端突触，未能成熟，和神经肌肉接头的总数保持constant.Conclusions：肌肉肥大mdx小鼠的结果从肌纤维分支，而不是肌纤维增生。
Background: Muscle hypertrophy in the mdx mouse model of Duchenne muscular dystrophy (DMD) can partially compensate for the loss of dystrophin by maintaining peak force production. Histopathology examination of the hypertrophic muscles suggests the hypertrophy primarily results from the addition of myofibers, and is accompanied by motor axon branching. However, it is unclear whether an increased number of innervated myofibers (myofiber hyperplasia) contribute to muscle hypertrophy in the mdx mice.Methods: To better understand the cellular mechanisms of muscle hypertrophy in mdx mice, we directly compared the temporal progression of the dystrophic pathology in the extensor digitorum longus (EDL) muscle to myofiber number, myofiber branching, and innervation, from 3 to 20 weeks of age.Results: We found that a 28% increase in the number of fibers in transverse sections of muscle correlated with a 31% increase in myofiber branching. Notably, the largest increases in myofiber number and myofiber branching occurred after 12 weeks of age when the proportion of myofibers with central nuclei had stabilized and the mdx mouse had reached maturity. The dystrophic pathology coincided with profound changes to innervation of the muscles that included temporary denervation of necrotic fibers, fragmentation of synapses, and ultra-terminal axon sprouting. However, there was little evidence of synapse formation in the mdx mice from 3 to 20 weeks of age. Only 4.4% of neuromuscular junctions extended ultra-terminal synapses, which failed to mature, and the total number of neuromuscular junctions remained constant.Conclusions: Muscle hypertrophy in mdx mice results from myofiber branching rather than myofiber hyperplasia.