Comparative proteomic analysis reveals the pathological mechanisms of overuse achilles tendinopathy and the therapeutic mechanisms of ESWT and PRP.
BACKGROUND: Achilles tendinopathy is a common musculoskeletal disorder with limited self-repair capacity. Although extracorporeal shock wave therapy (ESWT) and platelet-rich plasma (PRP) are widely used, their therapeutic mechanisms remain unclear. METHODS: A rat model of overuse Achilles tendinopathy was established by uphill treadmill running. Tendon morphology and structure were assessed by ultrasound and histology, and proteomic profiling was performed to identify differentially expressed proteins (DEPs) and enriched pathways. RESULTS: Ultrasound revealed subcutaneous edematous infiltration after overuse, and histology showed disorganized collagen fibers and altered cellular density. Compared with the normal group, the injury group showed 429 DEPs, which were enriched in pathways related to actin cytoskeleton and complement and coagulation cascades. Both ESWT and PRP treatments ameliorated these overuse-induced pathological changes. Compared with the rest group, the ESWT group showed 30 DEPs, while the PRP group showed 244, with 17 DEPs overlapping between the two comparisons. In the ESWT group, enriched pathways included actin cytoskeleton organization, protein stabilization, and sulfur metabolism. In the PRP group, enriched pathways included FcγR-mediated phagocytosis, lysosome, and endoplasmic reticulum protein processing. Compared with the normal group, the ESWT group showed 32 DEPs, whereas the PRP group showed only one (Serpina6), which was the only protein shared between the two comparisons. CONCLUSION: ESWT and PRP improve tendon healing in overuse Achilles tendinopathy through different molecular mechanisms. The PRP group showed a proteomic profile more similar to the normal group than the ESWT group. These findings provide a molecular basis for optimizing clinical treatment strategies.