Achilles tendon pain, tennis elbow and jumper's knee plague athletes and office workers alike, yet treatments remain scarce because the cause of tendinopathy has been murky. A team led by Jess Snedeker, professor of orthopaedic biomechanics at ETH Zurich and Balgrist University Hospital, and Katrien De Bock, professor of exercise and health, with doctoral student Greta Moschini as lead author, has now identified the transcription factor HIF1 as a central driver. The study appears in Science Translational Medicine.
Elevated HIF1 had been observed in diseased tendons before, but this work shows it actually causes the condition. In mice, permanently activating HIF1 produced tendon disease even without mechanical overload, while deactivating it in tendons prevented disease despite overloading. In tissue from surgical patients, higher HIF1 levels increased collagen crosslinks, leaving tendons more brittle, and encouraged blood vessels and nerves to grow into the tissue, which may explain the pain.
Because HIF1 also orchestrates the body's response to low oxygen, switching it off throughout the body would invite side effects. The researchers are therefore pursuing tendon-specific interventions and molecules downstream of HIF1 as potential drug targets. Early treatment matters: once the damage becomes irreversible, surgical removal of the affected tissue is currently the only option, making a first pharmacological therapy a significant prize.