A new study published in the journal Science reveals an exclusive form of cellular conversation that controls muscle repair. In damaged muscles, stem cells must work with immune cells to complete the repair process, but how these cells coordinate to ensure the efficient removal of dead tissue before making new muscle fibers remains unknown. Scientists have now shown that a natural substance called hyaluronic acid, used in cosmetics and injections for osteoarthritis, is the key molecule that manages this fundamental interaction.
“When muscle mass is damaged, it is essential that immune cells quickly enter the tissues and eliminate the damage before the stem cells begin to repair themselves,” said Dr. Jeffrey Dilworth, scientist principal at The Ottawa Hospital and professor at the University of Ottawa and senior author. on the study. “Our study shows that the muscle stem cells are ready to start repairing themselves immediately, but the immune cells keep the stem cells in a quiescent state while they finish the cleaning job. After approximately 40 hours, when the cleaning job is complete, an internal alarm goes off in the muscle stem cells, allowing them to wake up and start repairing themselves.”
Dr. Dilworth and his team have identified hyaluronic acid as the key ingredient in this internal wake-up call that tells muscle stem cells when to wake up. When muscle damage occurs, stem cells begin to produce and coat themselves with hyaluronic acid. Once the coating becomes thick enough, it blocks the immune cell signal to sleep and causes muscle stem cells to wake up.
Using mouse and human tissue , Dr. Dilworth and his team also discovered how muscle stem cells control the production of hyaluronic acid using epigenetic marks on the Has2 gene.
“It is Interestingly, aging is associated with chronic inflammation, muscle weakness, and a reduced ability of muscle stem cells to wake up and repair damage,” said lead author Dr. Kiran Nakka, associate of research of Dr. Dilworth who conducted this research as part of his postdoctoral studies. “If we could find a way to improve the production of hyaluronic acid in muscle stem cells of older people, it could help with muscle repair.”
The authors note that the regenerative effect of hyaluronic acid seems to depend on its production by muscle stem cells. The team is currently taking a look at whether drugs that alter the epigenetics of muscle stem cells could be used to increase their production of hyaluronic acid.