Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy, characterised by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle. For comparison, we also examined the similarly slowly progressing Myotonic Dystrophy type 2 (DM2). To investigate regeneration at the transcriptomic level, we first used the 200 human gene Hallmark Myogenesis list. This Myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myoblast counterparts, so is higher in myogenic differentiation. The Myogenesis biomarker was also elevated in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies compared to control biopsies, and on meta-analysis for each condition. The Myogenesis biomarker was also a robust binary discriminator of FSHD, DM2 and DMD from controls. We also analysed muscle regeneration at the protein level by immunolabelling muscle biopsies for Developmental Myosin Heavy Chain. Such immunolabelling revealed one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibialis anterior. The mean proportion of regenerating myofibres per quadriceps biopsy was 0.48%, significantly less that the 1.72% in the tibialis anterior. All DM2 muscle biopsies contained regenerating myofibres, with a mean of 1.24% per biopsy. Muscle regeneration in FSHD was correlated with the pathological hallmarks of fibre size variation, central nucleation, fibrosis and necrosis/regeneration/inflammation. In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pathology.

中文翻译：

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面肩肱型肌营养不良症的骨骼肌再生与病理严重程度相关。

面肩肱型肌营养不良症 (FSHD) 是一种常染色体显性肌病，其特征是缓慢进行性骨骼肌无力和消瘦。虽然在许多肌营养不良症中经常会引发再生反应，但人们对 FSHD 肌肉中是否会定期引发再生反应知之甚少。为了进行比较，我们还检查了类似缓慢进展的 2 型肌强直性营养不良 (DM2)。为了在转录组水平上研究再生，我们首先使用了 200 个人类基因 Hallmark Myogenesis 列表。与成肌细胞对应物相比，FSHD 和对照健康肌管中的这种肌生成生物标志物升高，因此肌源分化更高。在大多数独立 FSHD 的肌肉活检中，肌生成生物标志物也升高，DM2 或杜氏肌营养不良症 (DMD) 研究与对照活检进行比较，并针对每种情况进行荟萃分析。肌生成生物标志物也是 FSHD、DM2 和 DMD 与对照的强大二元鉴别器。我们还通过对发育性肌球蛋白重链的肌肉活检进行免疫标记，在蛋白质水平上分析了肌肉再生。这种免疫标记显示 76% 的股四头肌和 91% 的胫骨前肌活检组织中有一个或多个再生肌纤维。每次股四头肌活检的再生肌纤维的平均比例为 0.48%，明显低于胫骨前肌的 1.72%。所有 DM2 肌肉活检均含有再生肌纤维，每次活检平均为 1.24%。FSHD 的肌肉再生与纤维大小变化、中心成核、纤维化和坏死/再生/炎症。总之，FSHD 肌肉活检中的再生反应与病理的严重程度相关。