Advances in Understanding Skeletal Muscle Metabolism and Regeneration: From Mechanisms to Therapeutics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 1646

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Guest Editor
Department of Diagnostic and Health Sciences, College of Health Professions, The University of Tennessee Health Science Center, Memphis, TN, USA
Interests: aging; stroke; skeletal muscle atrophy, growth, regeneration, and metabolism; genomics; proteomics; metabolomics; bioinformatics
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Special Issue Information

Dear Colleagues,

Skeletal muscle, which accounts for 40% of total body weight, has diverse functions, including maintaining body posture and producing mobility and movement. Skeletal muscle is also essential for maintaining whole-body energy homeostasis, as it is involved in glucose and fatty acid metabolisms. Muscle tissue deteriorates with aging both quantitatively and qualitatively, which increases the risks of falls, osteoporosis, and metabolic diseases. Thus, maintaining muscle mass is important for a healthier life. Moreover, muscle mass can significantly impact the effects of various treatments, particularly in scenarios like cachexia, where a higher muscle mass often leads to better tolerance of treatment side effects and improved overall outcomes. In contrast, significant muscle loss (muscle wasting) can indicate poorer prognosis and increased toxicity due to reduced ability to withstand treatment stress; essentially, more muscle mass generally means better ability to cope with treatment demands. Therefore, maintaining muscle mass is important for whole-body metabolic homeostasis. Similarly, proper muscle regeneration is a key to maintaining muscle mass because it has been shown that muscle regeneration is significantly reduced in many disease and disorder conditions. We are looking for any kind of research manuscript that shows the data related to muscle metabolisms and regeneration.

Dr. Junaith S. Mohamed
Guest Editor

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Keywords

  • skeletal muscle
  • satellite cells
  • myoblast
  • myogenesis
  • regeneration
  • mitochondria
  • metabolism
  • sarcopenia
  • cachexia

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Published Papers (3 papers)

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Research

18 pages, 3940 KiB  
Article
CTCF Represses CIB2 to Balance Proliferation and Differentiation of Goat Myogenic Satellite Cells via Integrin α7β1–PI3K/AKT Axis
by Changliang Gong, Huihui Song, Zhuohang Hao, Zhengyi Zhang, Nanjian Luo and Xiaochuan Chen
Cells 2025, 14(15), 1199; https://doi.org/10.3390/cells14151199 - 5 Aug 2025
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Abstract
Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM–intracellular signaling. CIB2, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. [...] Read more.
Skeletal muscle development is a critical economic trait in livestock, governed by myogenic satellite cell regulation. Integrins mediate mechanical anchorage to the ECM and enable ECM–intracellular signaling. CIB2, as an EF-hand-domain protein involved in mechanotransduction, shows significant developmental regulation in goat muscle. Although the role of CIB2 in skeletal muscle growth is poorly characterized, we observed pronounced developmental upregulation of IB2 in postnatal goat muscle. CIB2 expression increased >20-fold by postnatal day 90 (P90) compared to P1, sustaining elevation through P180 (p < 0.05). Functional investigations indicated that siRNA-mediated knockdown of CIB2 could inhibit myoblast proliferation by inducing S-phase arrest (p < 0.05) and downregulating the expression of CDK4/Cyclin D/E. Simultaneously, CIB2 interference treatment was found to decrease the proliferative activity of goat myogenic satellite cells, yet it significantly promoted differentiation by upregulating the expression of MyoD/MyoG/MyHC (p < 0.01). Mechanistically, CTCF was identified as a transcriptional repressor binding to an intragenic region of the CIB2 gene locus (ChIP enrichment: 2.3-fold, p < 0.05). Knockdown of CTCF induced upregulation of CIB2 (p < 0.05). RNA-seq analysis established CIB2 as a calcium signaling hub: its interference activated IL-17/TNF and complement cascades, while overexpression suppressed focal adhesion/ECM–receptor interactions and enriched neuroendocrine pathways. Collectively, this study identifies the CTCF-CIB2–integrin α7β1–PI3K/AKT axis as a novel molecular mechanism that regulates the balance of myogenic fate in goats. These findings offer promising targets for genomic selection and precision breeding strategies aimed at enhancing muscle productivity in ruminants. Full article
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32 pages, 7206 KiB  
Article
From Development to Regeneration: Insights into Flight Muscle Adaptations from Bat Muscle Cell Lines
by Fengyan Deng, Valentina Peña, Pedro Morales-Sosa, Andrea Bernal-Rivera, Bowen Yang, Shengping Huang, Sonia Ghosh, Maria Katt, Luciana Andrea Castellano, Lucinda Maddera, Zulin Yu, Nicolas Rohner, Chongbei Zhao and Jasmin Camacho
Cells 2025, 14(15), 1190; https://doi.org/10.3390/cells14151190 - 1 Aug 2025
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Abstract
Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular [...] Read more.
Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article
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20 pages, 1740 KiB  
Article
Regulation of Myogenesis by MechanomiR-200c/FoxO3 Axis
by Junaith S. Mohamed and Aladin M. Boriek
Cells 2025, 14(12), 868; https://doi.org/10.3390/cells14120868 - 9 Jun 2025
Viewed by 547
Abstract
Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by [...] Read more.
Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast differentiation, and the introduction of the mechanomiR-200c antagomir restored the stretch effect. This suggests that stretch blocks differentiation, in part, through mechanomiR-200c. The gene encoding the transcription factor FoxO3 is a known direct target of mechanomiR-200c. Interestingly, MyoD binds to the mechanomiR-200c promoter in differentiating myoblasts, whereas stretch appears to reverse such binding. Our data further demonstrate that the levels of mechanomiR-200c are robustly elevated during the early stage of the muscle repair process in young mice, but not in the injured muscle of aged mice. Overall, we identified a novel pathway, MyoD/mechanomiR-200c/FoxO3a, and the potential mechanism by which stretch inhibits myoblast differentiation. Full article
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