The effect of galectin-1 on the differentiation of fibroblasts and myoblasts in vitro

2002 ◽  
Vol 115 (2) ◽  
pp. 355-366 ◽  
Author(s):  
Kirstin Goldring ◽  
Gareth E. Jones ◽  
Ramya Thiagarajah ◽  
Diana J. Watt
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Cell Line ◽  
Dermal Fibroblasts ◽  
Myogenic Cell ◽  
Mdx Mouse ◽  
Cytoskeletal Protein ◽  
Primary Myoblasts ◽  
Primary Mouse

Normal murine dermal fibroblasts implanted into the muscles of the mdx mouse, a model for Duchenne muscular dystrophy, not only participate in new myofibre formation but also direct the expression of the protein dystrophin which is deficient in these mice. We have reported that the lectin galectin-1 is implicated in the conversion of dermal fibroblasts to muscle. In the current work we confirm the presence of galectin-1 in the medium used for conversion. Furthermore we report that exposure of clones of dermal fibroblasts to this lectin results in 100% conversion of the cells. Conversion was assessed by the expression within the cells of the muscle-specific cytoskeletal protein desmin. We also investigate the effects of galectin-1 on cells of the C2C12 mouse myogenic cell line and on primary mouse myoblasts. Exposing both transformed and primary myoblasts to the lectin resulted in an increase in fusion of cells to the terminally differentiated state in both types of cultures. Galectin-1 does not cause the myogenic conversion of murine muscle-derived fibroblasts.

scholarly journals Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle

1995 ◽  
Vol 108 (1) ◽  
pp. 207-214 ◽  
Author(s):  
A.J. Gibson ◽  
J. Karasinski ◽  
J. Relvas ◽  
J. Moss ◽  
T.G. Sherratt ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Protein ◽  
Dermal Fibroblasts ◽  
Muscle Disease ◽  
Mdx Mouse ◽  
Muscle Fibres ◽  
Normal Muscle ◽  
Myogenic Cells ◽  
Mouse Muscle

Duchenne muscular dystrophy is a primary muscle disease that manifests itself in young boys as a result of a defect in a gene located on the X-chromosome. This gene codes for dystrophin, a normal muscle protein that is located beneath the sarcolemma of muscle fibres. Therapies to alleviate this disease have centred on implanting normal muscle precursor cells into dystrophic fibres to compensate for the lack of this gene and its product. To date, donor cells for implantation in such therapy have been of myogenic origin, derived from paternal biopsies. Success in human muscle, however, has been limited and may reflect immune rejection problems. To overcome this problem the patient's own myogenic cells, with the dystrophin gene inserted, could be used, but this could lead to other problems, since these cells are those that are functionally compromised by the disease. Here, we report the presence of high numbers of dystrophin-positive fibres after implanting dermal fibroblasts from normal mice into the muscle of the mdx mouse-the genetic homologue of Duchenne muscular dystrophy. Dystrophin-positive fibres were also abundant in mdx muscle following the implantation of cloned dermal fibroblasts from the normal mouse. Our results suggest the in vivo conversion of these non-myogenic cells to the myogenic pathway resulting in the formation of dystrophin-positive muscle fibres in the deficient host. The use of dermal fibroblasts may provide an alternative approach to the previously attempted myoblast transfer therapy, which in human trials has yielded disappointing results.

scholarly journals Functional and Molecular Effects of Arginine Butyrate and Prednisone on Muscle and Heart in the mdx Mouse Model of Duchenne Muscular Dystrophy

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e11220 ◽  
Author(s):  
Alfredo D. Guerron ◽  
Rashmi Rawat ◽  
Arpana Sali ◽  
Christopher F. Spurney ◽  
Emidio Pistilli ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Mdx Mouse ◽  
Molecular Effects ◽  
Arginine Butyrate

scholarly journals Differential Effects of Halofuginone Enantiomers on Muscle Fibrosis and Histopathology in Duchenne Muscular Dystrophy

2021 ◽  
Vol 22 (13) ◽  
pp. 7063
Author(s):  
Sharon Mordechay ◽  
Shaun Smullen ◽  
Paul Evans ◽  
Olga Genin ◽  
Mark Pines ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Motor Coordination ◽  
Mdx Mice ◽  
Cell Viability Assay ◽  
Muscle Fibrosis ◽  
Antifibrotic Therapy ◽  
Racemic Form ◽  
Viability Assay

Progressive loss of muscle and muscle function is associated with significant fibrosis in Duchenne muscular dystrophy (DMD) patients. Halofuginone, an analog of febrifugine, prevents fibrosis in various animal models, including those of muscular dystrophies. Effects of (+)/(−)-halofuginone enantiomers on motor coordination and diaphragm histopathology in mdx mice, the mouse model for DMD, were examined. Four-week-old male mice were treated with racemic halofuginone, or its separate enantiomers, for 10 weeks. Controls were treated with saline. Racemic halofuginone-treated mice demonstrated better motor coordination and balance than controls. However, (+)-halofuginone surpassed the racemic form’s effect. No effect was observed for (−)-halofuginone, which behaved like the control. A significant reduction in collagen content and degenerative areas, and an increase in utrophin levels were observed in diaphragms of mice treated with racemic halofuginone. Again, (+)-halofuginone was more effective than the racemic form, whereas (−)-halofuginone had no effect. Both racemic and (+)-halofuginone increased diaphragm myofiber diameters, with no effect for (−)-halofuginone. No effects were observed for any of the compounds tested in an in-vitro cell viability assay. These results, demonstrating a differential effect of the halofuginone enantiomers and superiority of (+)-halofuginone, are of great importance for future use of (+)-halofuginone as a DMD antifibrotic therapy.

Malignant Hyperthermia in a Child with Duchenne Muscular Dystrophy

PEDIATRICS ◽  
1983 ◽  
Vol 71 (1) ◽  
pp. 118-119
Author(s):  
HOWARD M. KELFER ◽  
WILLIAM D. SINGER ◽  
ROBERT N. REYNOLDS
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Side Effects ◽  
Muscular Dystrophy ◽  
Malignant Hyperthermia ◽  
Muscle Biopsy ◽  
Biopsy Specimen ◽  
Laboratory Findings ◽  
Anesthetic Agents ◽  
In Vitro Response

Patients with Duchenne muscular dystrophy (DMD) are susceptible to numerous adverse intraoperative and postoperative side effects of anesthetic agents. These include: hyperthermia and hyperkalemia,1,2 systemic acidosis,3 cardiac abnormalities (tachycardia, arrhythmia, arrest),2-5 rhabdomyolysis,2-6 as well as death.2,5 These clinical and laboratory findings are similar to those associated with malignant hyperthermia (MH).7,8 Until this time no one has confirmed the association of MH, as reflected by these clinical phenomena, in a patient with DMD. We present a patient who manifested many features of MH immediately following confirmatory muscle biopsy for DMD under general anesthesia. In vitro response to testing of a muscle biopsy specimen was consistent with a diagnosis of malignant hyperthermia.

scholarly journals Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junio Dort ◽  
Zakaria Orfi ◽  
Paul Fabre ◽  
Thomas Molina ◽  
Talita C. Conte ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gold Standard ◽  
Therapeutic Potential ◽  
Preclinical Study ◽  
Myogenic Cells ◽  
Inflammatory Phenotype ◽  
Myogenic Factors ◽  
Myogenic Progenitor Cells

AbstractLack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.

scholarly journals Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 61 ◽  
Author(s):  
Josiane Joseph ◽  
Dong Cho ◽  
Jason Doles
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Progenitor Cell ◽  
Treatment Options ◽  
Cell Types ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Metabolic Alterations ◽  
Potential Contributor

Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

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