A team of researchers led by Jess Snedeker, PhD, a professor of orthopedic biomechanics at ETH Zurich and Balgrist University Hospital in Zurich, both in Switzerland, and by Katrien De Bock, PhD, professor of exercise and health at ETH Zurich, has reached a new milestone in their studies of tendinopathy. In the HIF1 protein, 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.
This protein was already known to be at elevated levels in diseased tendons. Now, in experiments in mice and with tendon tissue from humans, the team of researchers has shown the conditions are actually triggered by the protein. Both in the mice and in the experiments with human tendon cells, they were able to show that elevated HIF1 levels in the tissue leads to a pathogenic remodeling of the tendons: More crosslinks form within the collagen fibers that make up the basic structure of the tendons.
“Our study not only provides new insight into how the disease develops,” said Snedeker. “It also shows that it’s important to treat tendon problems early … [as] the damage caused by HIF1 in tendon tissue can accumulate and become irreversible over time.”
The fact that HIF1 has now been identified as a molecular driver raises the question whether it is possible to develop medicines that deactivate HIF1 and therefore can prevent or cure tendon disease. It is not quite that easy, though, as in many organs of the body, HIF1 is responsible for detecting a lack of oxygen and activating a physiological adaptation, explained De Bock. However, it may be possible to look for methods that specifically deactivate HIF1 only in the tendon tissue.
