Adiponectin (ApN) is a hormone that exhibits anti-inflammatory effects on skeletal muscle exposed to acute and chronic inflammation. We have previously tested the implication of ApN in Duchenne muscular dystrophy (DMD) using mdx mice, a model of DMD, and by generating transgenic mdx mice overexpressing ApN. We showed that ApN can act as a preventive agent and delay disease progression by reducing muscle inflammation/injury and improving force/myogenesis. Herein, we took an opposite approach and crossed mdx mice with ApN knockout mice, to obtain mdx mice with ApN depletion. The aims were to test whether ApN deficiency could worsen the mdx phenotype and whether ApN supplementation can reverse several muscle abnormalities once the disease is settled. mdx-knockout mice exhibited lower muscle force/endurance as well as increased muscle damage when compared to regular mdx mice. Local administration of the ApN gene significantly reduced the expression of several oxidative stress/inflammatory markers and increased the expression of myogenic markers in the skeletal muscle. Finally, the presence of ApN markedly reduced the activity of NF-κB, a key player in muscle inflammation and myogenesis. ApN proves to be a powerful protector of the skeletal muscle capable of reversing the disease progression, thus making it a potential therapeutic agent for DMD.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.ajpath.2017.02.018 | DOI Listing |
Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need to identify novel targets to develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance of mitochondrial dynamics (fission and fusion) is crucial to maintain mitochondrial function and skeletal muscle health.
View Article and Find Full Text PDFNanoscale
January 2025
Department of Chemistry, Federal University of São Paulo (UNIFESP), Diadema, SP, Brazil.
This study aims to use superparamagnetic iron oxide nanoparticles (SPIONs), specifically magnetite (FeO), to deliver deflazacort (DFZ) and ibuprofen (IBU) to Duchenne muscular dystrophy-affected (DMD) mouse muscles using an external magnetic field. The SPIONs are synthesized by the co-precipitation method, and their surfaces are functionalized with L-cysteine to anchor the drugs, considering that the cysteine on the surface of the SPIONs in the solid state dimerizes to form the cystine molecule, creating the FeO-(Cys)-DFZ and FeO-(Cys)-IBU systems for tests. The FeO nanoparticles (NPs) were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and magnetic measurements.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
December 2024
Department of Biochemistry, Cell Biology and Microbiology, Mari State University, 424001 Yoshkar-Ola, Russia.
Objective: Ca overload of muscle fibers is one of the factors that secondarily aggravate the development of Duchenne muscular dystrophy (DMD). The purpose of this study is to evaluate the effects of the Ca channel modulator 2-aminoethoxydiphenyl borate (APB) on skeletal muscle pathology in dystrophin-deficient mice.
Methods: Mice were randomly divided into six groups: wild type (WT), WT+3 mg/kg APB, WT+10 mg/kg APB, , +3 mg/kg APB, +10 mg/kg APB.
J Proteomics
December 2024
School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia; Department of Medicine, University of Otago, Christchurch 8014, New Zealand; Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand. Electronic address:
Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female mdx mice were phenotypically stratified into "stress-resistant" or "stress-sensitive" groups based on their response to two laboratory stressors.
View Article and Find Full Text PDFJ 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.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!