Aerobic Exercise and Celastrol: A Promising Combination for Achilles Tendon Regeneration

Abstract

Background: Tendons are subjected to mechanical stress and strain during daily activities and physical exercise, which makes them susceptible to injury. Objectives: This randomized trial evaluated the effects of a 4-week combination of training and celastrol on the healing of Achilles tendon ruptures in rats. It assessed cytokine levels, gene expression, and histological changes. Methods: Rats with Achilles tendon ruptures were randomly assigned to several treatment groups: Sham, negative control, training, celastrol, and a combination of training and celastrol. Eligibility criteria included age, weight, and the absence of pre-existing tendon injuries. The assessments included enzyme-linked immunosorbent assay (ELISA) to measure cytokine levels [bFGF, IGF1, cyclooxygenase 2 (COX2)], real-time polymerase chain reaction (RT-PCR) to analyze gene expression (scleraxis, periostin, MMP9, collagen I), and histological analysis using Masson's trichrome staining to evaluate collagen organization. Results: The training-celastrol group exhibited the highest levels of bFGF, IGF1, and COX2, indicating a synergistic effect on tendon healing compared to the sham and negative control groups, with effect sizes of 0.85 (95% CI: 0.70 - 1.00). Additionally, RT-PCR results showed that the training-celastrol group had the highest expression of scleraxis, periostin, MMP9, and collagen I, suggesting enhanced tendon repair and remodeling. Histological analysis revealed that the training-celastrol group displayed the most organized collagen fibers, whereas the sham group showed regular organization, and the negative control group exhibited disorganized fibers. Conclusions: The study concluded that combining aerobic training and celastrol significantly enhances tendon healing by improving cytokine levels, gene expression, and collagen organization. Outcome measures were assessed at baseline, mid-treatment (week 2), and post-treatment (week 4) to evaluate temporal changes. These findings highlight the effectiveness of these therapeutic strategies in promoting tendon repair and maintaining structural integrity.