Trigger of Tendon Disease Discovered

Overuse of our tendons can cause painful medical conditions, known as tendinopathy. Researchers have now deciphered an important molecular mechanism that triggers these problems. Their findings will facilitate the development of new treatments.

A team of researchers led by Jess Snedeker, a professor of orthopedic biomechanics at ETH Zurich and Balgrist University Hospital in Zurich, and Katrien De Bock, professor of exercise and health at ETH Zurich, has reached a new milestone. In the HIF1 protein—which is known to be presented at elevated levels in diseased tendons—they have identified a central molecular driver of tendon problems of this kind. A part of HIF1 acts as a transcription factor, which controls the activity of genes in cells.

In mouse experiments, the researchers observed tendon disease even without overloading in the mice with permanently activated HIF1. No tendon disease occurred in the mice if HIF1 was deactivated in tendons, even in the case of overloading. Both in the mice and in the experiments with human tendon cells, they were able to show that due to elevated HIF1 levels in the tissue, more crosslinks form within the collagen fibers that make up the basic structure of the tendons, making the tendons more brittle and impairs their mechanical function. However, in many organs of the body, HIF1 is responsible for detecting a lack of oxygen and activating a physiological adaptation. Thus, “switching HIF1 off throughout the body would likely lead to side effects,” said DeBock.

It may be possible to look for methods that specifically deactivate HIF1 only in the tendon tissue. In DeBock’s view, the more promising approach would be to explore the biochemical processes around HIF1 in the cells in greater detail. This could help to identify other molecules that are influenced or controlled by HIF1 and that could be more suitable targets for the treatment of tendinopathy.