Mechanotransduction as a therapeutic target in tendinopathy: molecular pathways and exercise implications.

Abstract

Tendinopathy is a multifactorial condition driven by dysregulated mechanotransduction, chronic low-grade inflammation, oxidative stress, and impaired matrix homoeostasis. Despite its prevalence, current treatments focus largely on symptomatic relief, with limited impact on underlying pathology. This narrative review synthesizes emerging evidence on the molecular mechanisms underpinning tendinopathy, including integrin - FAK/Src, YAP/TAZ, and PIEZO1 signalling pathways, and highlights how these insights inform stage-specific rehabilitation strategies. In particular, isometric loading is explored as a biologically rational intervention, offering benefits in pain modulation, mechanosensitivity, and collagen synthesis. Additionally, novel therapies such as RNA-based interventions and mitochondrial antioxidants show promise in targeting cellular dysfunction. By bridging molecular pathophysiology with therapeutic application, this review underscores the need for personalized, mechanism-informed approaches to restore tendon health and improve clinical outcomes.