Sequential vascular and neural changes underlying the progression of patellar tendinopathy

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PURPOSE: To investigate the temporal sequence of vascular, neural, and extracellular matrix (ECM) changes during the progression of collagenase-induced patellar tendinopathy and to test the hypothesis that early angiogenesis initiates a cascade leading to neural remodeling and tendon degeneration. METHODS: A collagenase-induced rat patellar tendinopathy model was established in 40 male Sprague-Dawley rats. Animals were divided into one control group (PBS injection, n = 8, sacrificed at 12 weeks) and four experimental groups (collagenase type I injection, n = 8 each, sacrificed at 2, 4, 8, and 12 weeks post-injection). Histological evaluation (H&E and Masson's trichrome staining), immunohistochemistry, immunofluorescence (CD31, α-SMA, CGRP), and RT-qPCR for Col1a1, Col3a1, decorin (Dcn), and tenascin C (Tnc) were performed. Semi-quantitative scoring of cellularity, fibrosis, and vascularity was applied. Statistical analysis was conducted using ANOVA. RESULTS: Histology revealed progressive hypercellularity, fibrosis, and calcification, with significant increases in cellularity from week 8 and in vascularity from week 4. Immunofluorescence showed CD31-positive cells increasing significantly at week 4, followed by α-SMA-positive and CGRP-positive cells at week 8. mRNA analysis demonstrated early peaks of Col3a1, Dcn, and Tnc expression at 2 weeks, while Col1a1 expression peaked at 8 weeks and declined sharply by week 12. The Col1a1/Col3a1 ratio was significantly elevated at 8 weeks before decreasing at 12 weeks. CONCLUSION: This study demonstrates a sequential progression in collagenase-induced patellar tendinopathy, where early angiogenesis precedes neural remodeling and ECM turnover. These findings suggest that vascular remodeling may be associated with subsequent neural and structural changes during tendinopathy progression.