Biluo Qianyuan Formula Ameliorates Post-Traumatic Osteoarthritis by Suppressing FN1-Mediated Synovial Inflammation and Restoring Joint Homeostasis.

Background: Post-traumatic osteoarthritis (PTOA) lacks effective disease-modifying therapies that preserve joint structure while promoting tissue repair. This study aimed to evaluate the therapeutic efficacy and underlying mechanism of Biluo Qianyuan Formula (BLQYF), a standardized herbal formulation derived from clinical practice, as a potential disease-modifying alternative to celecoxib in a murine model of PTOA. Methods: A murine PTOA model was established and treated with BLQYF at different doses, with celecoxib serving as a pharmacological comparator. Safety was assessed by hepatic and renal toxicity analyses. Therapeutic effects were evaluated using micro-computed tomography (micro-CT) and histological staining. Network-based integrative analyses were conducted to identify key regulatory targets, followed by experimental validation in fibroblast-like synoviocytes. Results: BLQYF was well tolerated under the experimental conditions, with no detectable hepatic or renal toxicity at therapeutic doses. Micro-CT and histological analyses demonstrated that BLQYF dose-dependently mitigated subchondral bone deterioration, enhanced cartilage regeneration, and restored collagen deposition. At higher doses, BLQYF showed therapeutic efficacy comparable to celecoxib, with superior outcomes regarding cartilage reparation. Mechanistically, integrative analyses identified fibronectin 1 (FN1) as a central regulatory hub. Validation experiments confirmed that BLQYF suppressed FN1, MMP3, and TGF-β expression in fibroblast-like synoviocytes, thereby attenuating inflammation and extracellular matrix degradation. Conclusions: These findings support BLQYF as a promising disease-modifying therapeutic candidate for PTOA and highlight the fibroblast-FN1 axis as a novel pharmacological target for intervention.