Research ArticleTENDINOPATHY

Targeting the NF-κB signaling pathway in chronic tendon disease

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Science Translational Medicine  27 Feb 2019:
Vol. 11, Issue 481, eaav4319
DOI: 10.1126/scitranslmed.aav4319

Targeting tendinopathy

Inflammation and NF-κB signaling contribute to tendon degeneration and injury, such as rotator cuff injury. Abraham et al. investigated how this signaling pathway causes tendinopathy and potential therapeutic effects of inhibiting the pathway. Clinical tendon samples of human rotator cuff disease showed up-regulation of NF-κB, which was mimicked in mouse tendon fibroblasts overexpressing IKKβ. Genetic deletion of IKKβ in tendon in mice prevented maladaptive tendon remodeling in a treadmill running–induced overuse tendinopathy model and in a surgical model of tendon injury and repair, and human tendon stromal cells treated with an IKKβ inhibitor showed repressed NF-κB target gene transcription. These results suggest that there may be therapeutic potential in blocking IKKβ.

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