Xylosyltransferase-I in knee arthrofibrosis: Mechanistic insights and translational implications

Background: Arthrofibrosis is a frequent complication after total knee arthroplasty (TKA) and remains difficult to diagnose early due to the lack of reliable biomarkers. Excessive extracellular matrix (ECM) remodeling is driven by core signaling cascades, notably the Transforming Growth Factor-beta 1 (TGF-ß1) and Wnt/ß-catenin pathways. Xylosyltransferase-I (XT-I), a key enzyme regulating proteoglycan biosynthesis, has emerged as a critical downstream effector and potential indicator of early fibrotic activity. Methods: This narrative review summarizes clinical and experimental findings on XT-I in joint fibrosis, with emphasis on its role within the molecular network of key pro-fibrotic signaling and its diagnostic and translational potential in knee arthrofibrosis. Results: XT-I is consistently upregulated in fibrotic synovial fibroblasts and synovial fluid of arthrofibrotic knees, correlating with ECM remodeling and myofibroblast activation induced by both TGF-ß1and Wnt/ß-catenin signaling. XT-I demonstrates local rather than systemic diagnostic value and may serve as an early fibrosis indicator. Conclusion: XT-I holds promise as a synovial biomarker and potential therapeutic target in arthrofibrosis. Targeting XT-I, potentially in combination with core pathway inhibitors (e.g., Wnt/ß-catenin inhibitors), may offer a refined strategy for early diagnosis and postoperative management in TKA patients.