Defective satellite cells in congenital myotonic dystrophy

Furling, Denis; Coiffier, L.; Mouly, Vincent; Barbet, J. P.; Guily, Jean Lacau St; Taneja, Krishan; Gourdon, Geneviève; Junien, Claudine; Butler‐Browne, Gillian

doi:10.1093/hmg/10.19.2079

Cited by 103 publications

(106 citation statements)

References 47 publications

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“…Therefore, it seems that proliferation and differentiation are intrinsic features of the individual samples, and are not correlated with their disease status. In this respect, the HIBM primary myoblast cultures differ from those derived from myotonic dystrophy and HD patients, 18 that showed lower differentiation index than controls, and from congenital myotonic dystrophy (CMD), 19 and Duchenne muscular dystrophy (DMD) cells, 20,21 in which both proliferation and differentiation abilities are damaged. Thus, in these pathologies, basic biological functions of muscle satellite cells in culture are impaired.…”

Section: Discussionmentioning

confidence: 98%

“…The changes in apoptotic processes seen in HIBM satellite cells might be one of the initial pathologic events leading to the degeneration of muscle tissue, since they appear during the mitotic phase, while other biological functions of the cells -morphology, proliferation, senescence and differentiation -seem normal. In contrast, in highly degenerative diseases such as HD, CMD and DMD, most basic biological functions are impaired from the early stages of satellite cells activation, 17,19,21 and therefore even when apoptotic processes are involved, it is difficult to point to the initial steps of the process. Presently, the upstream events in HIBM pathophysiology, in terms of intracellular and intercellular signaling, have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of hereditary inclusion body myopathy myoblasts: possible primary impairment of apoptotic events

et al. 2007

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Hereditary inclusion body myopathy (HIBM) is a unique muscular disorder caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. GNE encodes a bi-functional enzyme acting in the biosynthetic pathway of sialic acid. Since the underlying myopathological mechanism leading to the disease phenotype is poorly understood, we have established human myoblasts cultures, derived from HIBM satellite cells carrying the homozygous M712T mutation, and identified cellular and molecular characteristics of these cells. HIBM and control myoblasts showed similar heterogeneous patterns of proliferation and differentiation. Upon apoptosis induction, phosphatidylserine externalization was similar in HIBM and controls. In contrast, the active forms of caspase-3 and -9 were strongly enhanced in most HIBM cultures compared to controls, while pAkt, downregulated in controls, remained high in HIBM cells. These results could indicate impaired apoptotic signaling in HIBM cells. Since satellite cells enable partial regeneration of the post-mitotic muscle tissue, these altered processes could contribute to the muscle mass loss seen in patients. The identification of survival defects in HIBM affected muscle cells could disclose new functions for GNE in muscle cells.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Characterization of hereditary inclusion body myopathy myoblasts: possible primary impairment of apoptotic events

et al. 2007

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“…52 The proliferative ability of FSHD myoblasts was also explored by the measurement of the telomere size. The length of the telomeric DNA is an indicator of cell proliferation, its measurement reflects the past divisions and is related to the remaining proliferation ability.…”

Section: Discussionmentioning

confidence: 99%

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Vilquin

Sacconi

et al. 2005

Gene Ther

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Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by a typical regional distribution, featuring composed patterns of clinically affected and unaffected muscles. No treatment is available for this condition, in which the pathophysiological mechanism is still unknown. Autologous transfer of myoblasts from unaffected to affected territories could be considered as a potential strategy to delay or stop muscle degeneration. To evaluate the feasibility of this concept, we explored and compared the growth and differentiation characteristics of myoblasts prepared from phenotypically unaffected muscles of five FSHD patients and 10 control donors. According to a clinically approved procedure, 10 9 cells of a high degree of purity were obtained within 16-23 days. More than 80% of these cells were myoblasts, as demonstrated by labeling of the muscle markers CD56 and desmin. FSHD myoblasts presented a doubling time equivalent to that of control cells; they kept high proliferation ability and did not show early telomere shortening. In vitro, these cells were able to differentiate and to express muscle-specific antigens. In vivo, they participated to muscle structures when injected into immunodeficient mice. These data suggest that myoblasts expanded from unaffected FSHD muscles may be suitable tools in view of autologous cell transplantation clinical trials.

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“…25,32 Here we showed that retrovirus producing (CUG) 13 antisense RNA has no effect on the proliferative rate of DM1 myoblasts; however, it restores the differentiation of infected DM1 myoblasts as indicated by the increase in the fusion index, in the mean number of nuclei per myotube as well as in the uptake of glucose. The specificity of these effects is supported by the fact that two other retrovirus producing the GFP protein or an antisense RNA against the 5 0 UTR have no effect on the levels of DMPK mRNAs nor on the growth and differentiation of DM1 myoblasts.…”

Section: Targeting Of Mutant Dmpk Transcripts D Furling Et Almentioning

confidence: 94%

“…The recovery of RNAs was determined by hybridization with a 32 Plabeled cyclophilin DNA probe as described. 32 DMPK probe was generated by random priming of 25-50 ng of the DMPK cDNA (BglII-SacI fragment) and hybridization was done overnight at 681C in hybridization buffer (2% SDS/10% dextran sulfate/1 Â SSPE/10 mg/ml salmon sperm DNA/2% Denhart's). Quantitation of relative RNA levels of autoradiograms was determined by densitometry (AlphaImager scan from Alpha Innovatech Corp.).…”

Section: Northern Blot Analysismentioning

confidence: 99%

Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions

Furling

Doucet²,

Ma³

et al. 2003

Gene Ther

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Myotonic dystrophy (DM1) is caused by the expansion of a trinucleotide repeat (CTG) located in the 3 0 untranslated region of the myotonic dystrophy protein kinase gene, for which currently there is no effective treatment. The data available suggest that misregulation of RNA homeostasis may play a major role in DM1 muscle pathogenesis. This indicates that the specific targeting of the mutant DMPK transcripts is essential to raise the rationale basis for the development of a specific gene therapy for DM1. We have produced a retrovirus which expresses a 149-bp antisense RNA complementary to the (CUG)13 repeats and to the 110-bp region following the repeats sequence to increase the specificity. This construct was introduced into human DM1 myoblasts, resulting in a preferential decrease in mutant DMPK transcripts, and effective restoration of human DM1 myoblast functions such as myoblast fusion and the uptake of glucose. It was previously shown that delay of muscle differentiation and insulin resistance in DM1 are associated with misregulation of CUGBP1 protein levels. The analysis of CUGBP1 levels and activity in DM1 cells expressing the antisense RNA indicated a correction of CUGBP1 expression in infected DM1 cells. We therefore show that current antisense RNA delivered in vitro using a retrovirus is not only capable of inhibiting mutant DMPK transcripts, but also can ameliorate dystrophic muscle pathology at the cellular levels. Gene Therapy (2003) 10, 795-802.

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Defective satellite cells in congenital myotonic dystrophy

Cited by 103 publications

References 47 publications

Characterization of hereditary inclusion body myopathy myoblasts: possible primary impairment of apoptotic events

Characterization of hereditary inclusion body myopathy myoblasts: possible primary impairment of apoptotic events

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions

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