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
Michelle is a health industry veteran who taught and worked in the field before training as a science journalist.
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