Brereton Daniel, Plochocki Jeffrey, An Daniel, Costas Jeffrey, Simons Erin
Arizona College of Osteopathic Medicine, Midwestern University.
PLoS Curr. 2012 Oct 10;4:e4ffdff160de8b. doi: 10.1371/4ffdff160de8b.
The development of spinal curvature deformities is a hallmark of muscular dystrophy. While glucocorticoid treatment has been shown to prolong muscle function in dystrophic mice, its effects on the development of dystrophinopathic spinal deformation are poorly understood. In this study, we test the effects of glucocorticoid treatment on the onset of thoracolumbar kyphosis in the dystrophin-deficient mdx mouse using voluntary running exercise to exacerbate muscle fibrosis. We measure the kyphotic index, erector spinae muscle fibrosis, and vertebral bone histomorphometry in 4-month-old mdx mice in four groups: sedentary control, exercise-treated (continuous voluntary access to an activity wheel), glucocorticoid-treated, and glucocorticoid + exercise-treated. Exercise treated mice were found to have significantly lower kyphotic index (i.e., greater kyphosis) and greater muscle fibrosis relative to controls (p < 0.05). However, the deleterious effect of exercise on KI and muscle fibrosis was prevented by glucocorticoid treatment. Some differences in bone histological parameters were observed between treatment groups, suggesting there is a complex relationship between dystrophic muscular changes and vertebral bone mass. Our findings indicate glucocorticoid treatment delays the onset of thoracodorsal spinal deformation in mdx mice.
脊柱弯曲畸形的发展是肌肉萎缩症的一个标志。虽然糖皮质激素治疗已被证明可延长营养不良小鼠的肌肉功能，但其对肌营养不良性脊柱变形发展的影响却知之甚少。在本研究中，我们使用自愿跑步运动加剧肌肉纤维化，来测试糖皮质激素治疗对肌营养不良蛋白缺陷型mdx小鼠胸腰段脊柱后凸症发病的影响。我们测量了四组4个月大的mdx小鼠的脊柱后凸指数、竖脊肌纤维化程度和椎骨组织形态计量学指标，这四组分别为：久坐对照组、运动治疗组（持续自愿使用活动轮）、糖皮质激素治疗组和糖皮质激素+运动治疗组。相对于对照组，运动治疗组小鼠的脊柱后凸指数显著更低（即后凸更严重），肌肉纤维化程度更高（p<0.05）。然而，糖皮质激素治疗可预防运动对脊柱后凸指数和肌肉纤维化的有害影响。在治疗组之间观察到了一些骨组织学参数的差异，这表明营养不良性肌肉变化与椎骨骨量之间存在复杂的关系。我们的研究结果表明，糖皮质激素治疗可延迟mdx小鼠胸背部脊柱变形的发病。
