Summary Athletic performance relies on tendons, which allow movement by transferring forces from the muscles to the skeleton. However, it is not understood how load-bearing structures in tendons sense and adapt to physical demands. Here, by performing calcium (Ca2+) imaging in mechanically loaded tendon explants from rats and in primary tendon cells from rats and humans, we show that tenocytes sense mechanical forces through the mechanosensitive ion channel PIEZO1, which senses stresses. cutting induced by collagen fiber. glide. Through loss-of-function and gain-of-function experiments targeting tenocytes in rodents, we show that reduced PIEZO1 activity decreased tendon stiffness and that the elevated PIEZO1 signaling mechanism increased tendon stiffness and strength, apparently by through upregulated collagen cross-linking. We also show that humans carrying the PIEZO1 E756del gain-of-function mutation show an average 13.2% increase in normalized jump height, presumably due to an increased rate of force generation or the release of a greater amount of energy. stored elastic. Further understanding of PIEZO1-mediated mechanoregulation of tendon stiffness should aid research in musculoskeletal medicine and sports performance. |
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Tendons are what connect muscles to bones. They are relatively thin but must withstand enormous forces. Tendons need a certain elasticity to absorb high loads, such as mechanical shock, without breaking. However, in sports that involve sprinting and jumping, stiff tendons are an advantage because they transmit the forces deployed in the muscles more directly to the bones.
Proper training helps to achieve optimal tendon stiffness.
Researchers from ETH Zurich and the University of Zurich, working at Balgrist University Hospital in Zurich, have now deciphered how tendon cells perceive mechanical stress and how they are able to adapt tendons to the demands of the body. Their findings have just been published in the journal Nature Biomedical Engineering [https://doi.org/10.1038/s41551-021-00716-x].
At the core of the newly discovered mechanism is a molecular force sensor in the tendon cells that consists of an ion channel protein. This sensor detects when the collagen fibers, which make up the tendons, move along each other. If such a strong shearing movement occurs, the sensor allows calcium ions to flow into the tendon cells. This promotes the production of certain enzymes that bind collagen fibers. As a result, the tendons lose elasticity and become stiffer and stronger.
Genetic variant overreacts
Interestingly, the ion channel protein responsible for this occurs in different genetic variants in humans. A few years ago, other scientists discovered that a particular variant called E756del clusters in individuals of West African ancestry . At that time, the importance of this protein for tendon stiffness was not yet known.
One-third of people of African descent carry this genetic variant, while it is rare in other populations.
This genetic variant protects its carriers from severe cases of malaria, a tropical disease. Scientists assume that the variant was able to prevail in this population because of this advantage.
Researchers led by Jess Snedeker, professor of orthopedic biomechanics at ETH Zurich and the University of Zurich, have now shown that mice carrying this genetic variant have stiffer tendons. They believe that the tendons "overshoot" their adaptive response to exercise due to this variant.
Big performance advantage
This also has direct effects on people’s ability to jump, as scientists demonstrated in a study with 65 African-American volunteers. Of the participants, 22 carried the E756del variant of the gene, while the remaining 43 did not. To take into account several factors that influence a person’s ability to jump (including physique, training, and general fitness), the researchers compared performance during a slow jump and a fast jump.
The tendons play only a minor role during slow jumping maneuvers, but are particularly important during fast jumps. With their study design, the scientists were able to isolate the effect of the genetic variant on jumping performance.
This showed that carriers of the E756del variant performed 13 percent better on average. "It is fascinating that a genetic variant, which is positively selected due to an anti-malaria effect, is at the same time associated with better athletic abilities. We certainly did not expect to find this when we started the project," says Fabian Passini. doctoral student in Snedeker’s group and first author of the study.
It may well be that this genetic variant partly explains why athletes who come from countries with a high frequency of E756del excel in world-class sports competitions, including sprinting, long jumping and basketball. To date, there has been no scientific research into whether this genetic variant is overrepresented among elite athletes. However, such a study would be of scientific interest, says Passini.
The findings on the force sensor and the mechanism by which tendons can adapt to physical demands are also important for physical therapy. "We now have a better understanding of how tendons work. This should also help us better treat tendon injuries in the future," says Snedeker. In the medium term, it may also be possible to develop drugs that engage the newly discovered tendon force sensor. These could one day help cure tendinopathies and other connective tissue disorders.
