Skip to content

Previously unknown mechanism in skeletal muscle regeneration identified.

Mammalian skeletal muscles can regenerate following injury and this response is mediated by a specific type of stem cell, the satellite cell.  Significant evidence suggests that while stem cells represent an important determinant for tissue regeneration, a qualified environment is necessary to guarantee and achieve functional results. It is therefore plausible that the loss of control over these cell fate decisions could lead to a pathological differentiation, leading to pathologic defects.  Now, researchers at the University of Louisville have identified a mechanism involved in skeletal muscle repair that may enable clinicians to boost the effectiveness of adult stem cell therapies for diseases such as muscular dystrophy. The team state that their findings describe the role of TNF receptor-associated factor 6 (TRAF6), an adaptor protein and E3 ubiquitin ligase, in ensuring the vitality of stem cells that regenerate muscle tissue.  The opensource study is published in the Journal of Clinical Investigation.

Previous studies show that specialized stem cells known as satellite cells reside in skeletal muscle in an inactive state. When muscle injury occurs, a complex chain of signals prompts the satellite cells to awaken and generate new muscle cells to repair the injury. Research has shown that Pax7, a paired-box transcription factor, is essential to this regeneration. When Pax7 is missing or reduced, the satellite cells undergo premature differentiation, or lose their stem properties and their ability to regenerate injured muscles.  In normal conditions, skeletal muscle is a self-healing tissue and can recover promptly from most trauma because of the satellite cells. However, in disease conditions like muscular dystrophies, satellite cells can’t keep up with repeated cycles of injury and are ultimately exhausted or functionally impaired.  The current study shows that removing TRAF6 depletes Pax7, resulting in reduced muscle regeneration in both normal and Duchenne muscular dystrophy mouse models.

The current study identifies a pathway by which the Pax7 and myogenic potential of satellite cells is regulated. Results show that the protein TRAF6 is a very important adaptor protein that is involved in multiple signaling pathways and its functions are important to maintain the stemness of satellite cells in adults.  The lab explain that this is because TRAF6 is upstream from Pax7 in the signaling process involved in muscle repair and orchestrates multiple signals controlling the muscle regeneration process.

The team surmise that their research ultimately will lead to improved treatments for muscle wasting diseases such as muscular dystrophy, ALS, cancer cachexia, diabetes, heart disease and others.  For the future, the researchers state that the next step is to see if this functional impairment is partially due to lack of TRAF6 signaling in satellite cells. They go on to conclude that if so, plan to take a patient’s stem cells, restore the TRAF6 activity, put them back and boost their regenerative potential.

Source: University of Louisville

TRAF6 fl/fl are control injured muscle. Credit: University of Louisville/Hindi and Kumar.
TRAF6 fl/fl are control injured muscle. Credit: University of Louisville/Hindi and Kumar.

 

 

Healthinnovations View All

Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.

Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.

Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

Leave a Reply

Translate »