Nintedanib reduces severity of post-traumatic joint contracture by modulating fibrosis and inflammation
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This study investigates the potential of nintedanib, a tyrosine kinase inhibitor with antifibrotic and anti-inflammatory properties, to mitigate post-traumatic joint contracture (PTJC) in a rat model. Given the lack of effective pharmacological treatments for this debilitating condition, this study aims to address the unmet need for non-surgical interventions by targeting the underlying fibrotic and inflammatory processes. A total of 26 male Sprague–Dawley rats were subjected to standardized knee trauma and immobilization for 2 weeks. Rats were randomized into two groups: a nintedanib treatment group (5 mg/kg taken twice daily, n = 13) and a placebo group (n = 13). Joint mobility was evaluated biomechanically by measuring the contracture angle (CA) and resistance to extension. Posterior joint capsule tissues were analyzed histologically and via qPCR for profibrotic gene expression, including α-Sma, Il-6, Tgf-β1, Nf-κb, and Ctgf. Nintedanib treatment significantly reduced CA compared to placebo (68.1° ± 12.6° vs. 84.8° ± 11.1°, p < 0.01), indicating improved joint mobility. Knee extension in the nintedanib-treated rats required less force, particularly at lower extension angles (p < 0.05). Molecular analysis showed a marked reduction in α-Sma expression, a myofibroblast marker, in the nintedanib group compared to placebo (11-fold decrease, p < 0.05). Histological examinations revealed relatively fewer myofibroblasts in the posterior joint capsule of rats treated with nintedanib. Nintedanib effectively mitigates fibrosis and inflammation in a rat model of PTJC, enhancing joint mobility and reducing profibrotic gene expression. These findings support further exploration of nintedanib as a pharmacological therapy for PTJC in clinical settings.
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Journal of molecular medicine, 103, Springer, Berlin ; Heidelberg ; New York, NY, 2025, https://doi.org/10.1007/s00109-025-02593-2