Cargando…

“The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies

The muscle stem cells niche is essential in neuromuscular disorders. Muscle injury and myofiber death are the main triggers of muscle regeneration via satellite cell activation. However, in degenerative diseases such as muscular dystrophy, regeneration still keep elusive. In these pathologies, stem...

Descripción completa

Detalles Bibliográficos
Autores principales: Cappellari, Ornella, Mantuano, Paola, De Luca, Annamaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407800/
https://www.ncbi.nlm.nih.gov/pubmed/32660168
http://dx.doi.org/10.3390/cells9071659
_version_ 1783567687872413696
author Cappellari, Ornella
Mantuano, Paola
De Luca, Annamaria
author_facet Cappellari, Ornella
Mantuano, Paola
De Luca, Annamaria
author_sort Cappellari, Ornella
collection PubMed
description The muscle stem cells niche is essential in neuromuscular disorders. Muscle injury and myofiber death are the main triggers of muscle regeneration via satellite cell activation. However, in degenerative diseases such as muscular dystrophy, regeneration still keep elusive. In these pathologies, stem cell loss occurs over time, and missing signals limiting damaged tissue from activating the regenerative process can be envisaged. It is unclear what comes first: the lack of regeneration due to satellite cell defects, their pool exhaustion for degeneration/regeneration cycles, or the inhibitory mechanisms caused by muscle damage and fibrosis mediators. Herein, Duchenne muscular dystrophy has been taken as a paradigm, as several drugs have been tested at the preclinical and clinical levels, targeting secondary events in the complex pathogenesis derived from lack of dystrophin. We focused on the crucial roles that pro-inflammatory and pro-fibrotic cytokines play in triggering muscle necrosis after damage and stimulating satellite cell activation and self-renewal, along with growth and mechanical factors. These processes contribute to regeneration and niche maintenance. We review the main effects of drugs on regeneration biomarkers to assess whether targeting pathogenic events can help to protect niche homeostasis and enhance regeneration efficiency other than protecting newly formed fibers from further damage.
format Online
Article
Text
id pubmed-7407800
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74078002020-08-12 “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies Cappellari, Ornella Mantuano, Paola De Luca, Annamaria Cells Review The muscle stem cells niche is essential in neuromuscular disorders. Muscle injury and myofiber death are the main triggers of muscle regeneration via satellite cell activation. However, in degenerative diseases such as muscular dystrophy, regeneration still keep elusive. In these pathologies, stem cell loss occurs over time, and missing signals limiting damaged tissue from activating the regenerative process can be envisaged. It is unclear what comes first: the lack of regeneration due to satellite cell defects, their pool exhaustion for degeneration/regeneration cycles, or the inhibitory mechanisms caused by muscle damage and fibrosis mediators. Herein, Duchenne muscular dystrophy has been taken as a paradigm, as several drugs have been tested at the preclinical and clinical levels, targeting secondary events in the complex pathogenesis derived from lack of dystrophin. We focused on the crucial roles that pro-inflammatory and pro-fibrotic cytokines play in triggering muscle necrosis after damage and stimulating satellite cell activation and self-renewal, along with growth and mechanical factors. These processes contribute to regeneration and niche maintenance. We review the main effects of drugs on regeneration biomarkers to assess whether targeting pathogenic events can help to protect niche homeostasis and enhance regeneration efficiency other than protecting newly formed fibers from further damage. MDPI 2020-07-09 /pmc/articles/PMC7407800/ /pubmed/32660168 http://dx.doi.org/10.3390/cells9071659 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cappellari, Ornella
Mantuano, Paola
De Luca, Annamaria
“The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title_full “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title_fullStr “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title_full_unstemmed “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title_short “The Social Network” and Muscular Dystrophies: The Lesson Learnt about the Niche Environment as a Target for Therapeutic Strategies
title_sort “the social network” and muscular dystrophies: the lesson learnt about the niche environment as a target for therapeutic strategies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407800/
https://www.ncbi.nlm.nih.gov/pubmed/32660168
http://dx.doi.org/10.3390/cells9071659
work_keys_str_mv AT cappellariornella thesocialnetworkandmusculardystrophiesthelessonlearntaboutthenicheenvironmentasatargetfortherapeuticstrategies
AT mantuanopaola thesocialnetworkandmusculardystrophiesthelessonlearntaboutthenicheenvironmentasatargetfortherapeuticstrategies
AT delucaannamaria thesocialnetworkandmusculardystrophiesthelessonlearntaboutthenicheenvironmentasatargetfortherapeuticstrategies