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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2014-09-22T00:00:00-04:00" class="date-display-single">September 22, 2014</span></p><div class='syndicate'><h1>Controlling Muscle Repair</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul class="spaced">
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<li>Researchers determined the role that the mouse protein Stat3 plays in regulating satellite cells, which are responsible for muscle regeneration.</li>
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<li>STAT3 inhibitors may improve skeletal muscle repair, thus offering a potential approach to treating muscle-wasting diseases.</li>
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<picture title="Illustration of muscle fibers">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=3paeAKqQ&timestamp=1431529221 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=aKavbw_L&timestamp=1431529221 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=Fk63H3wY&timestamp=1431529221 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=aCiTV4Vg&timestamp=1431529221 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=wWRDwm-M&timestamp=1431529221 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2014/20140922-muscle.jpg?itok=aKavbw_L&timestamp=1431529221" alt="Illustration of muscle fibers." title="Illustration of muscle fibers" />
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</picture><span class="caption">A Stat3 inhibitor improved muscle repair in mice. The results suggest a potential approach to treating muscle-wasting diseases in people.</span></div>
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</div><p>When skeletal muscle becomes damaged, the regeneration process involves a specialized population of cells called satellite cells. These cells normally lie dormant inside adult muscle. In response to injury or exercise, they become active and divide. Some satellite cells mature to replace the damaged muscle tissue, while others serve to replenish the pool of cells available for future repair.</p>
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<p>Following sustained cycles of repair, which occurs with aging and in muscle wasting diseases like muscular dystrophy, the normal regenerative process becomes impaired. This is thought to be due to a decline in the number and function of satellite cells.</p>
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<p>A team led by Dr. Alessandra Sacco at the Sanford-Burnham Medical Research Institute set out to explore the causes of satellite cell impairment and depletion. The research was funded in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Results appeared online on September 7, 2014, in <em>Nature Medicine</em>.</p>
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<p>Several muscle wasting conditions are characterized by chronic inflammation and activation of immune system molecules such as STAT3 (signal transducer and activator of transcription 3). The scientists found that when they induced muscle regeneration in mice, satellite cells were activated, and this was accompanied by activation of the mouse protein Stat3.</p>
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<p>When the team removed the <em>Stat3</em> gene from satellite cells, the number of satellite cells following muscle injury increased. However, regeneration was impaired. These findings suggested that Stat3 plays a role in the maturation of satellite cells into muscle cells.</p>
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||
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||
<p>In a series of experiments, the team went on to decipher the role of Stat3. This protein signals satellite cells to become, or differentiate, into mature muscle cells. The choice between self-renewal and differentiation creates a fine balance between maintaining a pool of satellite cells for future repairs and making muscle cells for current tissue repair. Manipulating the timing of Stat3 signals affects this balance.</p>
|
||
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||
<p>To see whether Stat3 might be a potential therapeutic target, the group analyzed models of impaired muscle regeneration. Inhibiting Stat3 in the regenerating muscles of aged mice accelerated tissue repair. In a mouse model of severe muscular dystrophy, in which muscle tissue undergoes repeated cycles of regeneration and degeneration, weekly treatment with a Stat3 inhibitor for a month improved muscle repair. The team also found that Stat3 inhibition promoted the proliferation of human muscle cells.</p>
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||
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||
<p>“Our study found that by introducing an inhibitor of the Stat3 protein in repeated cycles, we could alternately replenish the pool of satellite cells and promote their differentiation into muscle fibers,” Sacco says. STAT3 inhibitors are already being tested in clinical trials for other conditions such as cancer. With more development, these might be tested in clinical studies to treat muscle wasting.</p>
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<p>—by Carol Torgan, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/mechanism-muscle-loss-cancer" target="_top">The Mechanism of Muscle Loss in Cancer</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/blood-pressure-drug-may-help-muscle" target="_top">Blood Pressure Drug May Help Muscle</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/gene-could-hold-key-muscle-repair" target="_top">Gene Could Hold Key to Muscle Repair</a></li><li><a href="https://newsinhealth.nih.gov/issue/jul2013/feature1" target="_top">Healthy Movements: Your Body’s Mechanics</a></li><li><a href="http://www.niams.nih.gov/Health_Info/Kids/healthy_muscles.asp" target="_top">Healthy Muscles Matter</a></li><li><a href="http://www.ninds.nih.gov/disorders/md/md.htm" target="_top">Muscular Dystrophy</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/25194572">STAT3 signaling controls satellite cell expansion and skeletal muscle repair.</a> Tierney MT, Aydogdu T, Sala D, Malecova B, Gatto S, Puri PL, Latella L, Sacco A. <em>Nat Med.</em> 2014 Sep 7. doi: 10.1038/nm.3656. [Epub ahead of print]. PMID: 25194572.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Sanford-Burnham Center, California Institute for Regenerative Medicine (CIRM), and the Italian Foreign Ministry.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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