Wnt7a is required for regeneration of dystrophic skeletal muscle.

Autor: Gurriaran-Rodriguez U; Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.; CIC bioGUNE, Bizkaia Technology Park, Derio, 48160, Spain., Kodippili K; Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada., Datzkiw D; Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada., Javandoost E; Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada., Xiao F; Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, 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, ON, Canada. mrudnicki@ohri.ca.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. mrudnicki@ohri.ca.
Jazyk: angličtina
Zdroj: Skeletal muscle [Skelet Muscle] 2024 Dec 19; Vol. 14 (1), pp. 34. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1186/s13395-024-00367-x
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). Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver. We found that both WT and mdx mice lacking 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 decreased force generation prior to CTX injury. However, both WT and mdx muscle lacking Wnt7a displayed decreased force generation following CTX injection. Notably the regeneration deficit in mdx mice was rescued by a single tail vein injection of extracellular vesicles containing Wnt7a (Wnt7a-EVs). Therefore, we conclude that the regenerative capacity of muscle in mdx mice is highly dependant on the upregulation of endogenous Wnt7a following injury, and that systemic delivery of Wnt7a-EVs represents a therapeutic strategy for treating DMD.
Competing Interests: Declarations. Animal ethics approval: Housing, husbandry, and all experimental protocols for mice used in this study were performed in accordance with the guidelines established by the University of Ottawa Animal Care Committee, which is based on the guidelines of the Canadian Council on Animal Care. Committee’s reference number: 1. OHRIe-3868 - Experimental Protocol - Genetic Mouse Models for Investigating the Molecular Mechanisms of Muscle Regeneration [Expires June 30th, 2026]. 2. OHRIb-3826 - Breeding Protocol - Genetic Mouse Models for Investigating the Molecular Mechanisms of Muscle Regeneration [Expires March 31st, 2026]. Consent for publication: Not applicable. Competing interests: MAR is a co-inventor on patents pertaining to the use of Wnt7a to enhance muscle regeneration. The remaining authors declare no conflict of interest.
(© 2024. The Author(s).)
Databáze: MEDLINE
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