The extracellular matrix differentially directs myoblast motility and differentiation in distinct forms of muscular dystrophy: Dystrophic matrices alter myoblast motility

Ashlee M. Long, Jason M. Kwon, Ga Hyun Lee, Nina L. Reiser, Lauren A. Vaught, Joseph G. O'Brien, Patrick G.T. Page, Michele Hadhazy, Joseph C. Reynolds, Rachelle H. Crosbie, Alexis R. Demonbreun*, Elizabeth M. McNally*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)44-58
Number of pages15
JournalMatrix Biology
Volume129
DOIs
StatePublished - May 2024

Keywords

  • Annexin
  • Duchenne muscular dystrophy
  • Dysferlin
  • Extracellular matrix
  • Limb girdle muscular dystrophy
  • Muscle
  • Myoblast

ASJC Scopus subject areas

  • Molecular Biology

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