Wnt7a is Required for Regeneration of Dystrophic Skeletal Muscle.

Autor:	Gurriaran-Rodriguez U; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Kodippili K; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Datzkiw D; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Javandoost E; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Xiao F; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada., Rejas MT; Electron Microscopy Facility, Centro de Biología Molecular, Severo Ochoa. CSIC, Madrid, Spain., Rudnicki MA; Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 25. Date of Electronic Publication: 2024 Jan 25.
DOI:	10.1101/2024.01.24.577041
Abstrakt:	Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in mdx muscle, a model for Duchenne muscular dystrophy (DMD). However, loss-of-function studies to investigate the requirement for Wnt7a in muscle regeneration has not been evaluated. Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was specifically deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver. We found that both WT and mdx mice with deletion of Wnt7a in muscle, exhibited marked deficiencies in muscle regeneration at 21 d following cardiotoxin (CTX) induced injury. Unlike WT, deletion of Wnt7a in mdx resulted in a marked decrease in specific force generation prior to CTX injury. However, both WT and mdx muscle lacking Wnt7a displayed decreased specific force generation following CTX injection. Notably the regeneration deficit observed in mdx mice lacking Wnt7a in muscle was rescued by a single tail vein injection of an extracellular vesicle preparation containing Wnt7a (Wnt7a-EVs). Therefore, we conclude that the regenerative capacity of muscle in mdx mice is due to the upregulation of endogenous Wnt7a following injury, and that systemic delivery of Wnt7a-EVs represents a therapeutic strategy for treating DMD.
Databáze:	MEDLINE
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