Featured Research

from universities, journals, and other organizations

Scientists discover clues to muscle stem cell functions

Date:
May 15, 2012
Source:
Children's Hospital & Research Center Oakland
Summary:
Scientists have identified how skeletal muscle stem cells respond to muscle injury and may be stimulated to improve muscle repair in Duchenne Muscular Dystrophy, a severe inherited disease of muscle that causes weakness, disability and, ultimately, heart and respiratory failure.

A study conducted by Children's Hospital & Research Center Oakland scientists identifies how skeletal muscle stem cells respond to muscle injury and may be stimulated to improve muscle repair in Duchenne Muscular Dystrophy, a severe inherited disease of muscle that causes weakness, disability and, ultimately, heart and respiratory failure.

The study, led by Julie D. Saba, MD, PhD, senior scientist at Children's Hospital Oakland Research Institute (CHORI), shows that a lipid signaling molecule called sphingosine-1-phosphate or "S1P" can trigger an inflammatory response that stimulates the muscle stem cells to proliferate and assist in muscle repair. It further shows that mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, exhibit a deficiency of S1P, and that boosting their S1P levels improves muscle regeneration in these mice. A research report describing the study findings will be published online on May 14, 2012 in the journal Public Library of Science ONE (PLoS ONE).

Skeletal muscle is the biggest "organ" system of the human body. It is important for all human activity. Muscles can be injured by trauma, inactivity, aging and a variety of inherited muscle diseases. Importantly however, skeletal muscle is one of the few tissues of the human body that has the potential to fully repair itself after injury. The ability of muscles to regenerate themselves is attributed to the presence of a form of adult stem cells called "satellite cells" that are essential for muscle repair. Normally, satellite cells lie quietly at the periphery of the muscle fiber and do not grow, move or become activated. However, after muscle injury, these stem cells "wake up" through unclear mechanisms and fuse with the injured muscle, stimulating a complicated process that results in the rebuilding of a healthy muscle fiber.

S1P is a lipid signaling molecule that controls the movement and proliferation of many human cell types. Other scientists had shown previously that S1P can activate satellite cells, but they did not know how this occurred.

"We have been studying S1P signaling for many years," states Dr. Saba. "In 2003, we published a report demonstrating that fruit fly mutants with defective S1P metabolism were unable to fly because they developed a muscle disease or "myopathy" that led to degeneration of their flight muscles. Based on that observation, I became convinced that S1P signaling played an important role in muscle stability and homeostasis, not just in flies but in mammals, including humans."

Dr. Saba's team has discovered how S1P is able to "wake up" the stem cells at the time of injury. It involves the ability of S1P to activate S1P receptor 2, one of its five cell surface receptors, leading to downstream activation of an inflammatory pathway controlled by a transcription factor called STAT3. They showed that S1P is rapidly produced in the muscle immediately after injury, leading to an S1P "signal." S1P, acting through S1P receptor 2, leads to activation of STAT3, resulting in changes in gene expression that cause the satellite cell to leave its "sleeping" state and start to proliferate and assist in muscle repair.

"These findings are important especially for certain muscle diseases or "myopathies" that can affect children," states Dr. Saba. The most common and one of the most severe myopathies is Duchenne Muscular Dystrophy, a disease that affects young boys and often leads to death from respiratory and heart failure in a patient's twenties. Although patients with Duchenne Muscular Dystrophy start out life with enough satellite cells to repair the patients' degenerating muscles, over time the satellite cells fail to keep up with the rate of muscle degeneration. "We found that mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, are deficient in S1P. We were able to increase the S1P levels in the mice using a drug that blocks S1P breakdown. This treatment increased the number of satellite cells in the muscles and improved the efficiency of muscle regeneration after injury."

If these findings are also found to be true in humans with Duchenne Muscular Dystrophy, it may be possible to use similar approaches to boost S1P levels in order to improve satellite cell function and muscle regeneration in patients with the disease. Drugs that block S1P metabolism and boost S1P levels are now being tested for the treatment of other human diseases including rheumatoid arthritis. If these studies prove to be relevant in Duchenne patients, it may be possible to use the same drugs to improve muscle regeneration in these patients. Alternatively, new agents that can specifically activate S1P receptor 2 could also be beneficial in recruiting satellite cells and improving muscle regeneration in muscular dystrophy and potentially other diseases of muscle.

This work was supported by grants from the Muscular Dystrophy Association, the National Institutes of Health and a fellowship award from the California Institute of Regenerative Medicine.


Story Source:

The above story is based on materials provided by Children's Hospital & Research Center Oakland. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kenneth C. Loh, Weng-In Leong, Morgan E. Carlson, Babak Oskouian, Ashok Kumar, Henrik Fyrst, Meng Zhang, Richard L. Proia, Eric P. Hoffman, Julie D. Saba. Sphingosine-1-Phosphate Enhances Satellite Cell Activation in Dystrophic Muscles through a S1PR2/STAT3 Signaling Pathway. PLoS ONE, 2012; 7 (5): e37218 DOI: 10.1371/journal.pone.0037218

Cite This Page:

Children's Hospital & Research Center Oakland. "Scientists discover clues to muscle stem cell functions." ScienceDaily. ScienceDaily, 15 May 2012. <www.sciencedaily.com/releases/2012/05/120515070307.htm>.
Children's Hospital & Research Center Oakland. (2012, May 15). Scientists discover clues to muscle stem cell functions. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2012/05/120515070307.htm
Children's Hospital & Research Center Oakland. "Scientists discover clues to muscle stem cell functions." ScienceDaily. www.sciencedaily.com/releases/2012/05/120515070307.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins