Wnt7a is Required for Regeneration of Dystrophic Skeletal Muscle
Abstract Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression inmdxmuscle, 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) andmdxmice where Wnt7a was specifically deleted in muscle using a conditionalWnt7afloxed allele and aMyf5-Credriver. We found that both WT andmdxmice 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 inmdxresulted in a marked decrease in specific force generation prior to CTX injury. However, both WT andmdxmuscle lacking Wnt7a displayed decreased specific force generation following CTX injection. Notably the regeneration deficit observed inmdxmice 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 inmdxmice is due to the upregulation of endogenous Wnt7a following injury, and that systemic delivery of Wnt7a-EVs represents a therapeutic strategy for treating DMD..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 30. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gurriaran-Rodriguez, Uxia [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.24.577041 |
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| PPN (Katalog-ID): |
XBI042293006 |
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| 520 | |a Abstract Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression inmdxmuscle, 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) andmdxmice where Wnt7a was specifically deleted in muscle using a conditionalWnt7afloxed allele and aMyf5-Credriver. We found that both WT andmdxmice 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 inmdxresulted in a marked decrease in specific force generation prior to CTX injury. However, both WT andmdxmuscle lacking Wnt7a displayed decreased specific force generation following CTX injection. Notably the regeneration deficit observed inmdxmice 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 inmdxmice is due to the upregulation of endogenous Wnt7a following injury, and that systemic delivery of Wnt7a-EVs represents a therapeutic strategy for treating DMD. | ||
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| 700 | 1 | |a Javandoost, Ehsan |4 aut | |
| 700 | 1 | |a Xiao, Fan |4 aut | |
| 700 | 1 | |a Rejas, Maria Teresa |4 aut | |
| 700 | 1 | |a Rudnicki, Michael A. |0 (orcid)0000-0002-3866-5249 |4 aut | |
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