Tendinopathies — including Achilles pain, tennis elbow, swimmer’s shoulder and jumper’s knee — result from tendon overloading and can be hard to treat. A team led by Jess Snedeker and Katrien De Bock at ETH Zurich has identified a central molecular driver: a part of the HIF1 protein that functions as a transcription factor and alters gene activity in tendon cells.
The researchers combined mouse experiments with studies of human tendon tissue from surgeries. In mice, permanent activation of HIF1 produced tendon disease even without mechanical overload. Conversely, switching off HIF1 in tendons prevented disease despite overload. Together these experiments demonstrate that elevated HIF1 can be causal for tendinopathy.
At the tissue level, higher HIF1 led to pathogenic remodelling: increased crosslinking of collagen fibres made tendons more brittle and reduced mechanical function, while blood vessels and nerves grew into the tissue and could explain the associated pain. The authors stress that early treatment matters because HIF1‑driven damage can accumulate and become irreversible; in advanced cases physiotherapy may no longer help and surgery is the current option.
Identifying HIF1 as a driver raises the prospect of drug treatments, but De Bock warns that turning HIF1 off across the whole body could cause side effects because HIF1 senses low oxygen in many organs. The team plans to search for biochemical steps around HIF1 and for other molecules influenced by it that could be safer treatment targets. The research appears in Science Translational Medicine. Source: ETH Zurich.
Difficult words
- tendinopathy — painful disease of a tendonTendinopathies
- tendon — strong tissue connecting muscle to bonetendons
- transcription factor — protein that changes gene activity
- overload — to put too much force or workoverloading
- remodelling — process of structural change in tissue
- crosslinking — chemical bonds forming between fibres
- irreversible — impossible to return to earlier state
- physiotherapy — treatment using exercise and physical methods
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How might early diagnosis change outcomes for people with tendon pain, based on the article?
- What approaches could researchers use to target molecules around HIF1 to avoid whole-body side effects?
- Do you think physiotherapy or surgery is a better option when tendinopathy is advanced? Explain using reasons from the text.
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