The ability to move is an essential part of daily life. The locomotor, or musculoskeletal, system of the body consists of muscles, bones, tendons, ligaments, joints, cartilage and other connective tissue. Loss of motor function due to disease or injury can result in a lifetime of disability. In a rapidly aging society, maintaining and improving motor function can be a significant challenge for many people.
But there are ways to get around motor failure. As molecular biologists and orthopedic surgeons who study the locomotor system, we believe one key part of it has been underestimated – the tendons.
Tendons are tough tissues that connect muscle to bone. Tendons are what allow kangaroos to jump over 25 feet (7.62 meters) high and run up to 40 mph (64 kph). While their leg muscles are small, the kangaroos’ highly developed and long tendons act like powerful springs. People can also jump higher if they squat down first because their tendons store elastic energy that helps propel them upward.
In our research, we found that the presence of one particular protein in tendons plays a key role in how tendons heal – and a genetic mutation in that protein may also enhance athletic performance.
Tendons connect muscle to bone and are essential to movement.
Identifying tendon proteins
Tendon damage can be difficult to heal. Approximately 60% of tendon injuries lead to osteoarthritis, a disease resulting from the breakdown of the cartilage in joints that can make movement even more difficult.
Developing treatments for tendon injuries has likewise been challenging. One of the reasons is that the proteins controlling the genes instructing the body to create tendons, called transcription factors, had been unknown.
To identify these proteins, we created a catalog of the 1,600 transcription factors in the human body. Based on this catalog, we examined what genes were active in the Achilles tendon of genetically engineered mice and found that a protein called Mkx was a central transcription factor for the health of tendons.
Researchers have long considered tendons to be inert tissue unable to contract like muscles can. But one of our colleagues, Ardem Patapoutian, made the Nobel Prize-winning discovery that one particular protein on the surface of tendon cells, Piezo1, can sense when the tendon is engaging in moderate exercise and stimulate the Mkx transcription factor.
The discovery of Piezo1’s role in the perception of touch won the 2021 Nobel Prize in physiology or medicine.
Piezo1 and athletic performance
We then wondered about the role that Piezo1 plays in athletic performance. We were particularly interested in a variant of Piezo1 called E756del, which is found in around a third of people of African descent and thought to play a potential role in how high people can jump.
So we genetically…