Extracellular matrix (ECM) pathologic remodeling underlies many disorders, including muscular dystrophy. Tissue decellularization removes cellular components while leaving behind ECM components. We generated “on-slide” decellularized tissue slices from genetically distinct dystrophic mouse models. The ECM of dystrophin- and sarcoglycan-deficient muscles had marked thrombospondin 4 deposition, while dysferlin-deficient muscle had excess decorin. Annexins A2 and A6 were present on all dystrophic decellularized ECMs, but annexin matrix deposition was excessive in dysferlin-deficient muscular dystrophy. Muscle-directed viral expression of annexin A6 resulted in annexin A6 in the ECM. C2C12 myoblasts seeded onto decellularized matrices displayed differential myoblast mobility and fusion. Dystrophin-deficient decellularized matrices inhibited myoblast mobility, while dysferlin-deficient decellularized matrices enhanced myoblast movement and differentiation. Myoblasts treated with recombinant annexin A6 increased mobility and fusion like that seen on dysferlin-deficient decellularized matrix and demonstrated upregulation of ECM and muscle cell differentiation genes. These findings demonstrate specific fibrotic signatures elicit effects on myoblast activity.

中文翻译：

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细胞外基质在不同形式的肌营养不良中差异性地指导成肌细胞运动和分化：营养不良基质改变成肌细胞运动

细胞外基质（ECM）病理重塑是许多疾病的基础，包括肌营养不良症。组织脱细胞去除细胞成分，同时留下 ECM 成分。我们从遗传上不同的营养不良小鼠模型中生成了“载玻片上”脱细胞组织切片。肌营养不良蛋白和肌聚糖缺陷的肌肉的 ECM 有明显的血小板反应蛋白 4 沉积，而肌营养不良蛋白缺陷的肌肉则有过量的核心蛋白聚糖。膜联蛋白 A2 和 A6 存在于所有营养不良型脱细胞 ECM 上，但膜联蛋白基质沉积在 Dysferlin 缺陷型肌营养不良症中过量。膜联蛋白 A6 的肌肉定向病毒表达导致 ECM 中出现膜联蛋白 A6。接种到脱细胞基质上的 C2C12 成肌细胞表现出不同的成肌细胞迁移性和融合。缺乏抗肌营养不良蛋白的去细胞基质抑制成肌细胞的运动，而缺乏抗肌营养不良蛋白的去细胞基质则增强成肌细胞的运动和分化。用重组膜联蛋白 A6 处理的成肌细胞增加了活动性和融合，就像在缺乏 Dysferlin 的脱细胞基质上看到的那样，并证明了 ECM 和肌细胞分化基因的上调。这些发现表明特定的纤维化特征会对成肌细胞活性产生影响。