Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction

Submitted: 1 August 2014
Accepted: 9 October 2014
Published: 22 October 2014
Abstract Views: 1770
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Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are multisystemic disorders linked to two different genetic loci and characterized by several features including myotonia, muscle weakness and atrophy, cardiac dysfunctions, cataracts and insulin-resistance. In both forms, expanded nucleotide sequences cause the accumulation of mutant transcripts in the nucleus deregulating the activity of some RNAbinding proteins and providing an explanation for the multisystemic phenotype of DM patients. However this pathogenetic mechanism does not explain some histopathological features of DM skeletal muscle like muscle atrophy. It has been observed that DM muscle shares similarities with the ageing muscle, where the progressive muscle weakness and atrophy is accompanied by a lower regenerative capacity possibly due to the failure in satellite cells activation. The aim of our study is to investigate if DM2 satellite cell derived myoblasts exhibit a premature senescence as reported for DM1 and if alterations in their proliferation potential and differentiation capabilities might contribute to some of the histopathological features observed in DM2 muscles. Our results indicate that DM myoblasts have lower proliferative capability than control myoblasts and reach in vitro senescence earlier than controls. Differentely from DM1, the p16 pathway is not responsible for the premature growth arrest observed in DM2 myoblasts which stop dividing with telomeres shorter than controls. During in vitro senescence, a progressive decrease in fusion index is observable in both DM and control myotubes with no significant differences between groups. Moreover, myotubes obtained from senescent myoblasts appear to be smaller than those from young myoblasts. Taken together, our data indicate a possible role of DM2 premature myoblast senescence in skeletal muscle histopathological alterations i.e., dystrophic changes and type 2 fibre atrophy.

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Supporting Agencies

This research was funded by FMM-Fondazione Malattie Miotoniche, AFM-Association Francaise contre les Myopathies.
L.V. Renna, University of Milan
Department of Biosciences
R. Cardani, IRCCS-Policlinico San Donato, Milan
Laboratory of Muscle Histopathology and Molecular Biology,
A. Botta, Tor Vergata University of Rome
Department of Biomedicine and Prevention
G. Rossi, Tor Vergata University of Rome
Department of Biomedicine and Prevention
B. Fossati, University of Milan, IRCCS-Policlinico San Donato
Department of Biomedical Sciences for Health
E. Costa, IRCCS Policlinico San Donato, Milan
Service of Laboratory Medicine
G. Meola, University of Milan, IRCCS-Policlinico San Donato
Department of Biomedical Sciences for Health

How to Cite

Renna, L., Cardani, R., Botta, A., Rossi, G., Fossati, B., Costa, E., & Meola, G. (2014). Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction. European Journal of Histochemistry, 58(4). https://doi.org/10.4081/ejh.2014.2444