Symptom Duration-Dependent Protein Abundance Changes in Symptomatic and Asymptomatic Tendons in Early Stage...

Tendinopathy is a painful overuse disorder marked by a progressive functional decline. Although chronic disease mechanisms have been described, early molecular changes remain poorly defined. Here, we performed temporal proteomic profiling of human patellar tendon biopsies across one, two, and three months of symptom duration and evaluated proteome differences between symptomatic and nonsymptomatic contralateral tendons. Biopsies were collected from participants with unilateral patellar tendinopathy and symptoms lasting three months or less for analysis by data-independent acquisition liquid chromatography-mass spectrometry. Peptide- and protein-level abundances were quantified as part of a bottom-up proteomics workflow and assessed using two-way ANOVA with factors of symptom status and symptom duration. Symptom duration had a significant main effect: 12 proteins and 14 peptides changed significantly over time, with most peptides corresponding to the altered proteins. However, there was no interaction between the symptom status and symptom duration, no sex differences, and no detectable proteomic difference between symptomatic and contralateral tendons. These findings indicate that protein-level changes are detectable within the first three months of tendinopathy, and similar proteomic changes were also observed in contralateral tendons. Together, these observations suggest that early phase patellar tendinopathy is associated with time-dependent proteomic changes that are not confined to the symptomatic tendon.