origin-of-rare-disease-fop-rooted-in-muscle-regeneration-dysfunction

Origin of rare disease FOP rooted in muscle regeneration dysfunction

Image of control cells with normal muscle regeneration compared to cells with the same gene mutation as humans with FOP. Credit: Penn Medicine

Fibrodysplasia ossification (FOP) is a rare disease characterized by extensive bone growth outside the normal skeleton, preempting the body’s normal response even with minor injuries. The result is what is called a “second skeleton” that can fix joint movements and make breathing difficult. However, a new study of mice by a team at the University of Pennsylvania’s Perelman School of Medicine shows that the formation of extraskeletal bone may not be the only driver of the disease. Regeneration of impaired and inefficient muscle tissue appears to open up the possibility of unwanted bone formation in areas where new muscle should develop after an injury. This discovery opens up the possibility of pursuing new treatments for FOP today. npj regenerative medicine..

“We have made great strides to better understand the disease, but this study shows how basic biology can provide excellent insights into appropriate regenerative medicine therapies. “Masu,” said Dr. Foteini Mourkioti, the lead author of the study and an assistant professor of orthopedics. Co-Director of Cell and Developmental Biology, and Penn Regenerative Medicine Institute, Musculoskeletal Program. “We are now able to show from our lab that there is potential for a whole new therapeutic area for patients in this catastrophic condition.”

About 15 years ago, Penn researchers, including co-author of the study, Dr. Eileen Shore, a professor of orthopedics and genetics, and a co-director of the FOP and Related Disorders Research Center, found that mutations in the ACVR1 gene caused FOP. was. In that study, the team found that mutations alter cells in muscle and connective tissue, misorienting cells in tissue to behave like bone cells, resulting in new and unwanted extraskeletal bone in the body. I found.

“However, although extensive research has been conducted in recent years on how FOP mutations alter the regulation of cell fate decisions, the effects of genetic mutations on muscle and the effects on cells that repair muscle damage. Little attention has been paid to. “Shore said.” By advancing research in this area, we not only prevent the formation of excess bone, but also improve muscle function and regeneration, renewing the entire FOP. I was convinced that I could get clues to bring clear clarity. “

The researchers studied the muscles of mice with the same ACVR1 gene mutations as in FOP patients. They focused on two specific types of muscle tissue stem cells: fibrolipidogenic progenitor cells (FAP) and muscle stem cells (MuSC). Repairing muscle damage usually requires a careful balance between these two cell types. Damaged tissue responds by expanding FAP cells assigned to mobilize muscle stem cells to regenerate damaged muscle tissue. About three days later, the FAP disappeared and the work was done. At the same time, MuSC will move into a more mature and differentiated state. Muscle fiber, Essential for the systematic movement of our muscles.

Apoptosis-the process through which FAP passes in mice with the ACVR1 mutation studied by Mourkioti, Shore, and their co-authors. cell Die as part of proper muscle regeneration — significantly slower and increased presence of FAP beyond normal lifespan. This changed the balance with MuSC. Damaged tissue also showed reduced maturation capacity of muscle stem cells, resulting in significantly smaller muscle fibers in mice with the ACVR1 mutation compared to muscle fibers in unmutated mice.

“Long-term persistence of diseased FAP in regenerating muscle contributes to changes in the muscular environment of FOP. logic It regenerates and allows excess FAP to contribute to the formation of extraskeletal bone. This gives a whole new perspective on how excess extraskeletal bone is formed and can be prevented. “

Current goals for treating FOP focus on slowing the growth of extraskeletal bone. This research has the potential to provide a crucial new direction. “We suggest that therapeutic interventions should be considered to promote muscle regenerative capacity with reduced ectopicity. Bone “By addressing both the stem cell population and their role in the origin of FOP, treatment can be significantly enhanced,” said Shore and Murchioti.

Other authors of this study include Alexandra Stanley, Elysiaticy, Jacob Cocan, and Douglas Roberts.



For more information:

Dynamics of stem cells present in skeletal muscle during myogenesis in progressive ossifying fibrodysplasia, npj regenerative medicine, 2022.

Quote: The origin of FOP, a rare disease rooted in muscle regeneration dysfunction (January 14, 2022), is from https://medicalxpress.com/news/2022-01-rare-disease-fop-rooted-muscle.html 2022 Obtained on January 14, 2014

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Origin of rare disease FOP rooted in muscle regeneration dysfunction Source link Origin of rare disease FOP rooted in muscle regeneration dysfunction

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