Artikel
Protective effect of tranexamic acid on the progression of post-traumatic osteoarthritis in the murine ACLT model
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Veröffentlicht: | 23. Oktober 2023 |
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Gliederung
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Objectives: Post-traumatic osteoarthritis (OA) is a common disorder that imposes significant physical and psychological burdens on affected patients. Tranexamic acid (TXA), the most widely utilized antifibrinolytic agent, is commonly employed in orthopedic trauma surgery and has been demonstrated to modulate inflammatory responses and bone cell function, both of which are disturbed during OA disease progression. This study aimed to evaluate the impact of systemic and topical TXA treatment on the progression of post-traumatic knee OA in a standardized pre-clinical mouse model.
Methods: Post-traumatic OA was established by performing anterior cruciate ligament transection (ACLT) of the right knee in adult female mice. Mice were treated with TXA or vehicle intra-peritoneally daily or intra-articularly weekly for 4 weeks, starting at the day of surgery. Bilateral knee joints from mice were harvested for micro-CT scanning and histology. Histopathological alternations were assessed through scoring of articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation. Subchondral bone microstructure and osteophyte volume were quantified using micro-CT evaluation. Cartilage thickness and osteoblast/osteoclast parameters were assessed histomorphometrically. Data were analyzed by one-way or two-way ANOVA test as appropriate, followed by Tukey's post-hoc tests.
Results and conclusion: Both systemic and topical treatment with TXA caused a significant reduction in scores of cartilage degeneration, synovitis, and bone erosion. Furthermore, a pronounced increase was observed in the ratio of hyaline to calcified cartilage thickness after both TXA treatment regimes. Micro-CT analysis showed that systemic TXA was effective in reversing subchondral bone loss and inhibiting osteophyte formation induced by ACLT, whereas topical treatment had no effect. Additionally, histomorphometric analysis revealed that systemic TXA resulted in a decrease in the number and surface area of osteoclasts in subchondral bone, while having no effect on osteoblast parameters. Neither osteoclasts nor osteoblasts parameters were considerably altered following topical administration of TXA. Collectively, these findings suggest that both systemic and topical TXA exhibit protective effects on the progression of ACLT-induced OA in mice, suggesting TXA application as a novel and promising approach for preventing or treating post-traumatic OA.