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Cells
Special Issues
Regulatory Programs of Skeletal Muscle Repair and Regeneration
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Regulatory Programs of Skeletal Muscle Repair and Regeneration

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 7119

Special Issue Editors

Prof. Dr. Chiara Sassoli

E-Mail Website1 Website2
Guest Editor
Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, Imaging Platform, University of Florence, Florence, Italy
Interests: anatomy, skeletal muscle tissue repair and regeneration; fibrosis; regenerative medicine; stromal cells; photobiomodulation, platelet rich plasma
Prof. Dr. Roberta Squecco

E-Mail Website1 Website2
Guest Editor
Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
Interests: skeletal muscle, smooth muscle, gap junctions, myotubes, ion channels, electrophysiology, adipokines, stem cells, excitation contraction coupling, damage, bioactive lipids, muscle atrophy, neurons

Special Issue Information

Dear Colleagues,

Adult healthy skeletal muscle possesses a robust capability to repair/regenerate. This is mediated by its resident stem cells, called satellite cells (SCs) on account of their position at the periphery of the host myofiber. SC behavior is finely regulated by both intrinsic (pre-programmed signaling pathways, telomerase functionality, epigenetic adaptive changes) and extrinsic mechanisms (mutual paracrine/juxtacrine interactions that SCs establish with niche, mechanical stimuli). Stromal interstitial cells are emerging as integral to an efficient muscle repair/regeneration. Usually, upon a focal damage, an adaptive reparative fibrotic (transient) response occurs, compliant with SC proper functionality, sustaining their progression into the myogenic program and the morpho-functional recovery of injured muscle. Conversely, in severely/persistently damaged or pathological muscles, the niche conveys instructive signals, skewing the fate of unhealthy muscles toward fibro-adipogenic degeneration that is not conducive for SC functionality, often already compromised in these conditions. Despite the recent advances, some aspects of this inherent muscle program are unclear. Thus, renewed efforts are required to provide novel mechanistic insights into the complex network orchestrating SC activity and into degeneration/regeneration (un)balance. This Special Issue welcomes studies that will improve the current knowledge on this fascinating topic and that may certainly offer cues for smart therapeutic target identification.

Prof. Dr. Chiara Sassoli
Prof. Dr. Roberta Squecco
Guest Editors

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Published Papers (2 papers)

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Research

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25 pages, 6258 KiB  
Article
HIF-1α/MMP-9 Axis Is Required in the Early Phases of Skeletal Myoblast Differentiation under Normoxia Condition In Vitro
by Flaminia Chellini, Alessia Tani, Martina Parigi, Francesco Palmieri, Rachele Garella, Sandra Zecchi-Orlandini, Roberta Squecco and Chiara Sassoli
Cells 2023, 12(24), 2851; https://doi.org/10.3390/cells12242851 - 16 Dec 2023
Cited by 2 | Viewed by 1690
Abstract
Hypoxia-inducible factor (HIF)-1α represents an oxygen-sensitive subunit of HIF transcriptional factor, which is usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expressions. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has [...] Read more.
Hypoxia-inducible factor (HIF)-1α represents an oxygen-sensitive subunit of HIF transcriptional factor, which is usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expressions. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as a SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. Herein, using biomolecular, biochemical, morphological and electrophysiological analyses, we analyzed HIF-1α expression, localization and role in differentiating murine C2C12 myoblasts and SCs under normoxia. In addition, we evaluated the role of matrix metalloproteinase (MMP)-9 as an HIF-1α effector, considering that MMP-9 is involved in myogenesis and is an HIF-1α target in different cell types. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression. Differently, the more differentiated elongated and parallel-aligned cells, which are likely ready to fuse with each other, show a mainly cytoplasmic localization of the factor. Multinucleated myotubes displayed both nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. By means of silencing HIF-1α and MMP-9 by short-interfering RNA and MMP-9 pharmacological inhibition, this study unraveled MMP-9’s role as an HIF-1α downstream effector and the fact that the HIF-1α/MMP-9 axis is essential in morpho-functional cell myogenic commitment. Full article
(This article belongs to the Special Issue Regulatory Programs of Skeletal Muscle Repair and Regeneration)
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Review

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11 pages, 960 KiB  
Review
The Multiple Roles of Lactate in the Skeletal Muscle
by Bianca Bartoloni, Michele Mannelli, Tania Gamberi and Tania Fiaschi
Cells 2024, 13(14), 1177; https://doi.org/10.3390/cells13141177 - 10 Jul 2024
Viewed by 4383
Abstract
Believed for a long time to be merely a waste product of cell metabolism, lactate is now considered a molecule with several roles, having metabolic and signalling functions together with a new, recently discovered role as an epigenetic modulator. Lactate produced by the [...] Read more.
Believed for a long time to be merely a waste product of cell metabolism, lactate is now considered a molecule with several roles, having metabolic and signalling functions together with a new, recently discovered role as an epigenetic modulator. Lactate produced by the skeletal muscle during physical exercise is conducted to the liver, which uses the metabolite as a gluconeogenic precursor, thus generating the well-known “Cori cycle”. Moreover, the presence of lactate in the mitochondria associated with the lactate oxidation complex has become increasingly clear over the years. The signalling role of lactate occurs through binding with the GPR81 receptor, which triggers the typical signalling cascade of the G-protein-coupled receptors. Recently, it has been demonstrated that lactate regulates chromatin state and gene transcription by binding to histones. This review aims to describe the different roles of lactate in skeletal muscle, in both healthy and pathological conditions, and to highlight how lactate can influence muscle regeneration by acting directly on satellite cells. Full article
(This article belongs to the Special Issue Regulatory Programs of Skeletal Muscle Repair and Regeneration)
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