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Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction
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 sequence...
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Published in: | European journal of histochemistry 2014-10, Vol.58 (4), p.2444-2444 |
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creator | Renna, L V Cardani, R Botta, A Rossi, G Fossati, B Costa, E Meola, G |
description | 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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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.</description><identifier>ISSN: 1121-760X</identifier><identifier>EISSN: 2038-8306</identifier><identifier>DOI: 10.4081/ejh.2014.2444</identifier><identifier>PMID: 25578974</identifier><language>eng</language><publisher>Italy: PAGEPress Publications</publisher><subject>aging ; Cells, Cultured ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis ; Female ; Gene Expression Regulation ; Humans ; Male ; Muscle Fibers, Skeletal - metabolism ; Muscle Fibers, Skeletal - pathology ; Muscle Proteins - biosynthesis ; myoblasts ; Myotonic dystrophy ; Myotonic Dystrophy - metabolism ; Myotonic Dystrophy - pathology ; Original Paper ; p16 ; telomeres</subject><ispartof>European journal of histochemistry, 2014-10, Vol.58 (4), p.2444-2444</ispartof><rights>Copyright PAGEPress Publications 2014</rights><rights>Copyright L.V. Renna et al. 2014 Licensee PAGEPress, Italy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-16e5f471b1768ebf6bc68f94428d3051e6eb0bd9e6152c58b0ff105a55294a403</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289846/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1648335457?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25578974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Renna, L V</creatorcontrib><creatorcontrib>Cardani, R</creatorcontrib><creatorcontrib>Botta, A</creatorcontrib><creatorcontrib>Rossi, G</creatorcontrib><creatorcontrib>Fossati, B</creatorcontrib><creatorcontrib>Costa, E</creatorcontrib><creatorcontrib>Meola, G</creatorcontrib><title>Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction</title><title>European journal of histochemistry</title><addtitle>Eur J Histochem</addtitle><description>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.</description><subject>aging</subject><subject>Cells, Cultured</subject><subject>Cellular Senescence</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Male</subject><subject>Muscle Fibers, Skeletal - metabolism</subject><subject>Muscle Fibers, Skeletal - pathology</subject><subject>Muscle Proteins - biosynthesis</subject><subject>myoblasts</subject><subject>Myotonic dystrophy</subject><subject>Myotonic Dystrophy - metabolism</subject><subject>Myotonic Dystrophy - pathology</subject><subject>Original Paper</subject><subject>p16</subject><subject>telomeres</subject><issn>1121-760X</issn><issn>2038-8306</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqFks-P1CAUxxujccfVo1dD4sVLR6BA6cXEbPyxySZ60MQbofCYYdKWLtA1899LnXHjevFE4H3fJ-99v1TVS4K3DEvyFg77LcWEbSlj7FG1obiRtWyweFxtCKGkbgX-cVE9S-mAsejK7Wl1QTlvZdeyTXX7NcKo8xIBJZggGZgMID-hOfpRxyMal2QGQGYZVlFCwaHxGHKYvEH2mHIM8_6I8nEGRJFPaAoZ6ZSC8TqDRT993qOZiIK0i8k-TM-rJ04PCV6cz8vq-8cP364-1zdfPl1fvb-pDeck10QAd6wlPWmFhN6J3gjpOsaotA3mBAT0uLcdCMKp4bLHzhHMNee0Y5rh5rK6PnFt0Ad1XkcF7dXvhxB3Ssfsy3KqlcRqDdJJZhnmXd-RjjmwjJpiEmkK692JNS_9CLaYlKMeHkAfVia_V7twp8q0nWSiALZngN7BXHxM980EqzVIVYJUa5BqDbI0vDk3xHC7QMpq9CWcYdAThCUpIhinDca0K9LX_0gPYYlT8XZVyabhjLdFVZ9UJoaUIrj_DvDq75Xv1X--TvMLkPnEXA</recordid><startdate>20141022</startdate><enddate>20141022</enddate><creator>Renna, L V</creator><creator>Cardani, R</creator><creator>Botta, A</creator><creator>Rossi, G</creator><creator>Fossati, B</creator><creator>Costa, E</creator><creator>Meola, G</creator><general>PAGEPress Publications</general><general>PAGEPress Publications, Pavia, Italy</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>67V</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141022</creationdate><title>Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction</title><author>Renna, L V ; 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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.</abstract><cop>Italy</cop><pub>PAGEPress Publications</pub><pmid>25578974</pmid><doi>10.4081/ejh.2014.2444</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | aging Cells, Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis Female Gene Expression Regulation Humans Male Muscle Fibers, Skeletal - metabolism Muscle Fibers, Skeletal - pathology Muscle Proteins - biosynthesis myoblasts Myotonic dystrophy Myotonic Dystrophy - metabolism Myotonic Dystrophy - pathology Original Paper p16 telomeres |
title | Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is not associated with p16 induction |
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