P4.23 The role of activin receptor IIB signalling on skeletal muscle and the possible therapeutic implication for Duchenne muscular dystrophy

2011 ◽  
Vol 21 (9-10) ◽  
pp. 711 ◽  
Author(s):  
E. Mouisel ◽  
I. Barthélémy ◽  
A. Ferry ◽  
L. Garcia ◽  
S. Blot ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Implication ◽  
Activin Receptor ◽  
Activin Receptor Iib

scholarly journals Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin

2017 ◽  
Vol 74 (13) ◽  
pp. 2487-2501 ◽  
Author(s):  
S. Lecompte ◽  
M. Abou-Samra ◽  
R. Boursereau ◽  
L. Noel ◽  
S. M. Brichard
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Anti Inflammatory

Characterisation of dystrophin during development of human skeletal muscle

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 395-402 ◽  
Author(s):  
A. Clerk ◽  
P.N. Strong ◽  
C.A. Sewry
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Human Skeletal Muscle ◽  
Gradual Increase ◽  
Differential Staining ◽  
Relative Molecular Mass ◽  
Adult Tissue ◽  
Dmd Gene

Dystrophin, the 427 × 10(3) Mr product of the Duchenne muscular dystrophy (DMD) gene, was studied in human foetal skeletal muscle from 9 to 26 weeks of gestation. Dystrophin could be detected from at least 9 weeks of gestation at the sarcolemmal membrane of most myotubes, though there was differential staining with antibodies raised to various regions of the protein. Dystrophin immunostaining increased and became more uniform with age and by 26 weeks of gestation there was intense sarcolemmal staining of all myotubes. On a Western blot, a doublet of smaller relative molecular mass than that seen in adult tissue was detected in all foetuses studied. There was a gradual increase in abundance of the upper band from 9 to 26 weeks, and the lower band, although present in low amounts in young foetuses, increased significantly between 20 and 26 weeks of gestation. These data indicate that there are several specific isoforms of dystrophin present in developing skeletal muscle, though the role of these is unknown.

scholarly journals DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies

2020 ◽  
Vol 29 (17) ◽  
pp. 2855-2871
Author(s):  
Andrea L Reid ◽  
Yimin Wang ◽  
Adrienne Samani ◽  
Rylie M Hightower ◽  
Michael A Lopez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Function ◽  
Myogenic Differentiation ◽  
Nucleotide Exchange ◽  
Dystrophic Muscle ◽  
Guanine Nucleotide Exchange ◽  
Myogenic Factors

Abstract DOCK3 is a member of the DOCK family of guanine nucleotide exchange factors that regulate cell migration, fusion and viability. Previously, we identified a dysregulated miR-486/DOCK3 signaling cascade in dystrophin-deficient muscle, which resulted in the overexpression of DOCK3; however, little is known about the role of DOCK3 in muscle. Here, we characterize the functional role of DOCK3 in normal and dystrophic skeletal muscle. Utilizing Dock3 global knockout (Dock3 KO) mice, we found that the haploinsufficiency of Dock3 in Duchenne muscular dystrophy mice improved dystrophic muscle pathologies; however, complete loss of Dock3 worsened muscle function. Adult Dock3 KO mice have impaired muscle function and Dock3 KO myoblasts are defective for myogenic differentiation. Transcriptomic analyses of Dock3 KO muscles reveal a decrease in myogenic factors and pathways involved in muscle differentiation. These studies identify DOCK3 as a novel modulator of muscle health and may yield therapeutic targets for treating dystrophic muscle symptoms.

scholarly journals Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Sugihara ◽  
Naomi Teramoto ◽  
Katsuyuki Nakamura ◽  
Takanori Shiga ◽  
Taku Shirakawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Mesenchymal Progenitor Cells

Abstract Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients. Senescence was induced in satellite cells and mesenchymal progenitor cells, owing to the increased expression of CDKN2A, p16- and p19-encoding gene. Genetic ablation of p16 in DMD rats dramatically restored body weight and muscle strength. Histological analysis showed a reduction of fibrotic and adipose tissues invading skeletal muscle, with increased muscle regeneration. Senolytic drug ABT263 prevented loss of body weight and muscle strength, and increased muscle regeneration in rats even at 8 months—the late stage of DMD. Moreover, senescence markers were highly expressed in the skeletal muscle of DMD patients. In situ hybridization of CDKN2A confirmed the expression of it in satellite cells and mesenchymal progenitor cells in patients with DMD. Collectively, these data provide new insights into the integral role of senescence in DMD progression.

The Role of Exercise as a Therapy for Children with Duchenne Muscular Dystrophy

2000 ◽  
Vol 12 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Stephen P. Sayers
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Premature Death ◽  
Risks And Benefits ◽  
Progressive Weakness

Duchenne muscular dystrophy (DMD) is a disease affecting muscle fiber integrity in boys that leads to progressive weakness in skeletal muscle and premature death. Currently, there is no known cure for the disease. Different interventions have been explored to delay the progression of the disease and improve the quality of life for the DMD patient. Physical activity is one treatment that has generated controversy due to the increased mechanical stress placed on the muscle during contraction. This review explores the literature in animal models and human DMD patients and evaluates the known theoretical risks and benefits of increased physical activity in DMD patients.

Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

2021 ◽  
pp. 1-5
Author(s):  
Gian Luca Vita ◽  
Luisa Politano ◽  
Angela Berardinelli ◽  
Giuseppe Vita
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Systematic Investigation ◽  
Mdx Mice ◽  
True Incidence ◽  
Patients With Cancer ◽  
Dmd Gene ◽  
Age Range ◽  
Prevalence Of Cancer

Background: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD. Methods: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years. Results: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old. Conclusion: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

A carrier of Duchenne muscular dystrophy with dilated cardiomyopathy but no skeletal muscle symptom

1995 ◽  
Vol 17 (3) ◽  
pp. 202-205 ◽  
Author(s):  
Hirotoshi Kinoshita ◽  
Yu-ichi Goto ◽  
Mitsuru Ishikawa ◽  
Tetsuya Uemura ◽  
Kouichi Matsumoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Muscle Symptom
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