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Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.
J Cachexia Sarcopenia Muscle
February 2025
Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.
Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.
Short-chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice.
J Cachexia Sarcopenia Muscle
December 2024
Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Background: Sarcopenia is a prevalent muscle disorder in old people leading to higher fracture rate, mortality, and other adverse clinical outcomes. Evidence indicates that short-chain fatty acids (SCFAs), which are beneficial gut microbial metabolites, were reduced in old people with sarcopenia. This study aimed to determine whether the use of SCFAs as a supplement can be a therapeutic strategy of sarcopenia in a pre-clinical model.
View Article and Find Full Text PDFMyosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle.
J Physiol
October 2024
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM.
View Article and Find Full Text PDFSingle-cell RNA-seq reveals novel interaction between muscle satellite cells and fibro-adipogenic progenitors mediated with FGF7 signalling.
J Cachexia Sarcopenia Muscle
August 2024
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, China.
Article Synopsis
- - The study investigates how muscle satellite cells (MuSCs) interact with surrounding niche cells to influence muscle adaptation, using single-cell RNA sequencing on porcine muscles to uncover various cell types and their functions.
- - Researchers identified five main cell types, including myogenic cells and fibro-adipogenic progenitors (FAPs), and discovered six subpopulations of myogenic cells, with notable differences in cell composition between muscle types.
- - FGF7 was shown to enhance MuSC proliferation, with significant increases in cell numbers observed after FGF7 treatment, indicating its crucial role in muscle repair and growth through interactions with FAPs.
Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6.
J Cachexia Sarcopenia Muscle
August 2024
Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil.
Background: The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. The mechanisms that interconnect both processes at the transcriptional level remain underexplored. Nr2f6, a nuclear receptor, regulates metabolism and cell differentiation in peripheral tissues.
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