Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury

Abstract Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers. We recently identified secreted ADA...

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Main Authors: Nandaraj Taye, Levon Rodriguez, James C. Iatridis, Woojin M. Han, Dirk Hubmacher
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-024-00383-x
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author Nandaraj Taye
Levon Rodriguez
James C. Iatridis
Woojin M. Han
Dirk Hubmacher
author_facet Nandaraj Taye
Levon Rodriguez
James C. Iatridis
Woojin M. Han
Dirk Hubmacher
author_sort Nandaraj Taye
collection DOAJ
description Abstract Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers. We recently identified secreted ADAMTS-like 2 (ADAMTSL2) as a pro-myogenic regulator of muscle development, where it promoted myoblast differentiation. Since myoblast differentiation is a key process in skeletal muscle regeneration, we here examined the role of ADAMTSL2 during muscle regeneration after BaCl2 injury. Specifically, we found that muscle regeneration was delayed after ablation of ADAMTSL2 in myogenic precursor cells and accelerated following injection of pro-myogenic ADAMTSL2 protein domains. Mechanistically, ADAMTSL2 regulated the number of committed myoblasts, which are the precursors for myocytes and regenerating myofibers. Collectively, our data support a role for myoblast-derived ADAMTSL2 as a positive regulator of muscle regeneration and provide a proof-of-concept for potential therapeutic applications.
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spelling doaj-art-bc1b2c2d16a141d09f67b221f021ac6f2025-08-20T02:31:38ZengNature Portfolionpj Regenerative Medicine2057-39952024-12-019111510.1038/s41536-024-00383-xMyoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injuryNandaraj Taye0Levon Rodriguez1James C. Iatridis2Woojin M. Han3Dirk Hubmacher4Orthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount SinaiOrthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount SinaiOrthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount SinaiOrthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount SinaiOrthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount SinaiAbstract Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers. We recently identified secreted ADAMTS-like 2 (ADAMTSL2) as a pro-myogenic regulator of muscle development, where it promoted myoblast differentiation. Since myoblast differentiation is a key process in skeletal muscle regeneration, we here examined the role of ADAMTSL2 during muscle regeneration after BaCl2 injury. Specifically, we found that muscle regeneration was delayed after ablation of ADAMTSL2 in myogenic precursor cells and accelerated following injection of pro-myogenic ADAMTSL2 protein domains. Mechanistically, ADAMTSL2 regulated the number of committed myoblasts, which are the precursors for myocytes and regenerating myofibers. Collectively, our data support a role for myoblast-derived ADAMTSL2 as a positive regulator of muscle regeneration and provide a proof-of-concept for potential therapeutic applications.https://doi.org/10.1038/s41536-024-00383-x
spellingShingle Nandaraj Taye
Levon Rodriguez
James C. Iatridis
Woojin M. Han
Dirk Hubmacher
Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
npj Regenerative Medicine
title Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
title_full Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
title_fullStr Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
title_full_unstemmed Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
title_short Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury
title_sort myoblast derived adamts like 2 promotes skeletal muscle regeneration after injury
url https://doi.org/10.1038/s41536-024-00383-x
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