Purpose <p>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.</p> Methods <p>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&#xa0;weeks) and four experimental groups (collagenase type I injection, n = 8 each, sacrificed at 2, 4, 8, and 12&#xa0;weeks post-injection). Histological evaluation (H&amp;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.</p> Results <p>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 <i>Col3a1</i>, <i>Dcn</i>, and <i>Tnc</i> expression at 2&#xa0;weeks, while <i>Col1a1</i> expression peaked at 8&#xa0;weeks and declined sharply by week 12. The <i>Col1a1/Col3a1</i> ratio was significantly elevated at 8&#xa0;weeks before decreasing at 12&#xa0;weeks.</p> Conclusion <p>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.</p>

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Sequential vascular and neural changes underlying the progression of patellar tendinopathy

  • Jinsung Park,
  • Naoki Takemoto,
  • Tae-Hwan Kim,
  • Junsuke Nakase,
  • Jin Kyu Lee

摘要

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.