Celecoxib Disrupts Temporal Coordination of TGF-β/α-SMA Signaling in Skeletal Muscle Repair: A Time-Dependent Study of Fibrosis and Inflammation

This study investigates the time-dependent effects of the selective COX-2 inhibitor celecoxib on skeletal muscle regeneration, aiming to clarify its role in balancing inflammation and fibrosis—a critical controversy in COX-2 inhibitor applications. Using a C57BL/6 mouse model of blunt-impact gastrocnemius muscle injury, researchers divided 72 mice into normal, model (injury + saline), and celecoxib (injury + 100 mg/kg celecoxib) groups, collecting tissue samples at 3, 7, 14, and 21 days post-injury. Analyses included hematoxylin-eosin and Masson staining for histopathology, immunohistochemistry for α-SMA and TGF-β, immunofluorescence for COX-2, and Western blot for protein quantification.Key findings revealed that celecoxib significantly reduced early-phase inflammation (3–7 days; p These results highlight a dual role for celecoxib: it mitigates early inflammation but may impair late-stage tissue maturation due to prolonged TGF-β suppression and disrupted myofibroblast regulation. The study concludes that time-restricted celecoxib administration is critical in muscle injury therapy, emphasizing the need to balance acute symptom control with long-term functional recovery to optimize therapeutic outcomes.