Muscle Biology Group, Department of Animal Sciences, University of Arizona, Tucson, AZ 85724, USA; Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
Biochem Biophys Res Commun. 2013 Oct 25;440(3):399-404. doi: 10.1016/j.bbrc.2013.09.085. Epub 2013 Sep 23.
Deficits in skeletal muscle function exist during aging and muscular dystrophy, and suboptimal function has been related to factors such as atrophy, excessive inflammation and fibrosis. Ineffective muscle regeneration underlies each condition and has been attributed to a deficit in myogenic potential of resident stem cells or satellite cells. In addition to reduced myogenic activity, satellite cells may also lose the ability to communicate with vascular cells for coordination of myogenesis and angiogenesis and restoration of proper muscle function. Objectives of the current study were to determine the angiogenic-promoting capacity of satellite cells from two states characterized by dysfunctional skeletal muscle repair, aging and Duchenne muscular dystrophy. An in vitro culture model composed of satellite cells or their conditioned media and rat adipose tissue microvascular fragments (MVF) was used to examine this relationship. Microvascular fragments cultured in the presence of rat satellite cells from adult muscle donors (9-12 month of age) exhibited greater indices of angiogenesis (endothelial cell sprouting, tubule formation and extensive branching) than MVF co-cultured with satellite cells from aged muscle donors (24 month of age). We sought to determine if the differential degree of angiogenesis we observed in the co-culture setting was due to soluble factors produced by each satellite cell age group. Similar to the co-culture experiment, conditioned media produced by adult satellite cells promoted greater angiogenesis than that of aged satellite cells. Next, we examined differences in angiogenesis-stimulating ability of satellite cells from 12 mo old MDX mice or age-matched wild-type mice. A reduction in angiogenesis activity of media conditioned by satellite cells from dystrophic muscle was observed as compared to healthy muscle. Finally, we found reduced gene expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in both aged and dystrophic satellite cells compared to their adult and normal counterparts, respectively. These results indicate that functional deficits in satellite cell activities during aging and diseased muscle may extend to their ability to communicate with other cells in their environment, in this case cells involved in angiogenesis.
骨骼肌功能在衰老和肌肉营养不良时存在缺陷，并且功能不佳与萎缩、过度炎症和纤维化等因素有关。每种情况下都存在无效的肌肉再生，这归因于驻留干细胞或卫星细胞的成肌潜能缺陷。除了成肌活性降低之外，卫星细胞还可能失去与血管细胞进行通信的能力，从而无法协调肌生成和血管生成以及恢复适当的肌肉功能。本研究的目的是确定两种功能失调的骨骼肌修复状态（衰老和杜氏肌营养不良症）下的卫星细胞的促血管生成能力。使用由卫星细胞或其条件培养基和大鼠脂肪组织微血管片段（MVF）组成的体外培养模型来检查这种关系。在存在来自成年肌肉供体（9-12 月龄）的大鼠卫星细胞的情况下培养的微血管片段表现出比与来自老年肌肉供体（24 月龄）的卫星细胞共培养的微血管片段更高的血管生成指数（内皮细胞发芽、管形成和广泛分支）。我们试图确定在共培养环境中观察到的不同程度的血管生成是否是由于每个卫星细胞年龄组产生的可溶性因子。与共培养实验相似，来自成年卫星细胞的条件培养基促进了比来自老年卫星细胞的条件培养基更高的血管生成。接下来，我们检查了来自 12 月龄 MDX 小鼠或年龄匹配的野生型小鼠的卫星细胞的促血管生成能力的差异。与健康肌肉相比，来自萎缩肌肉的卫星细胞产生的培养基的血管生成活性降低。最后，我们发现与成年和正常对照相比，衰老和营养不良的卫星细胞中缺氧诱导因子 1α（HIF-1α）和血管内皮生长因子（VEGF）的基因表达降低。这些结果表明，衰老和患病肌肉中卫星细胞活性的功能缺陷可能会扩展到它们与环境中其他细胞（在这种情况下是参与血管生成的细胞）进行通信的能力。
