ETH Zurich scientists led by Jess Snedeker and Katrien De Bock discovered the HIF1 protein as a central trigger of tendon diseases such as Achilles, tennis elbow and jumper's knee.[1][2][3] HIF1 acts as a transcription factor that regulates the activity of specific genes in tendon cells.[1][2][3] Previous studies found elevated levels of HIF1 in damaged tendons, but research has shown that the protein directly causes the disease.[1][2][3] In experiments on mice with HIF1 permanently on, tendons were damaged even without overloading, while disabling HIF1 protected tendons from disease even when overloaded.[1][2][3] A study of human tendon cells obtained from surgery showed that high levels of HIF1 cause harmful changes in tendon structure.[1][2][3] Specifically, there is the formation of a greater number of cross-links in the collagen fibers that form the basic structure of the tendons and reduce their strength.[1][2][3] These findings confirm the causal relationship of HIF1 to degenerative changes in tendons.[1][2][3]