1. The extracellular matrix differentially directs myoblast motility and differentiation in distinct forms of muscular dystrophy: Dystrophic matrices alter myoblast motility.
- Author
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Long, Ashlee, Long, Ashlee, Kwon, Jason, Lee, GaHyun, Reiser, Nina, Vaught, Lauren, OBrien, Joseph, Page, Patrick, Hadhazy, Michele, Demonbreun, Alexis, McNally, Elizabeth, Crosbie, Rachelle, Reynolds, Joseph, Long, Ashlee, Long, Ashlee, Kwon, Jason, Lee, GaHyun, Reiser, Nina, Vaught, Lauren, OBrien, Joseph, Page, Patrick, Hadhazy, Michele, Demonbreun, Alexis, McNally, Elizabeth, Crosbie, Rachelle, and Reynolds, Joseph
- Abstract
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.
- Published
- 2024