Human xylosyltransferases – mediators of arthrofibrosis? New pathomechanistic insights into arthrofibrotic remodeling after knee replacement therapy

• Published in: Scientific reports Vol. 5; no. 1; p. 12537
• Main Authors: Faust, Isabel, Traut, Philipp, Nolting, Frank, Petschallies, Jan, Neumann, Elena, Kunisch, Elke, Kuhn, Joachim, Knabbe, Cornelius, Hendig, Doris
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.07.2015; Nature Publishing Group
• Subjects: 13/106; 13/21; 13/51; 38; 38/77; 38/90; 631/45; 692/308/1892; 82/58; Actin; Actins - genetics; Actins - metabolism; Aged; Arthroplasty, Replacement, Knee - adverse effects; Biosynthesis; Case-Control Studies; Collagen (type III); Enzyme Activation - drug effects; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Fibroblasts; Fibroblasts - metabolism; Fibrosis; Galectin 3 - blood; Galectin-3; Gene expression; Gene Expression Regulation; Growth Differentiation Factor 15 - blood; Humanities and Social Sciences; Humans; Joint diseases; Joint Diseases - etiology; Joint Diseases - metabolism; Joint Diseases - pathology; Knee; Knee Joint - metabolism; Knee Joint - pathology; Middle Aged; multidisciplinary; Pentosyltransferases - blood; Pentosyltransferases - genetics; Pentosyltransferases - metabolism; Range of Motion, Articular; Risk Factors; Science; Serum levels; Smooth muscle; Transforming growth factor; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; UDP Xylose-Protein Xylosyltransferase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep12537

Total knee replacement (TKR) is a common therapeutic option to restore joint functionality in chronic inflammatory joint diseases. Subsequent arthrofibrotic remodeling occurs in 10%, but the underlying pathomechanisms remain unclear. We evaluated the association of xylosyltransferases (XT), fibrotic mediators catalyzing glycosaminoglycan biosynthesis, leading to arthrofibrosis as well as the feasibility of using serum XT activity as a diagnostic marker. For this purpose, synovial fibroblasts (SF) were isolated from arthrofibrotic and control synovial biopsies. Basal α-smooth muscle actin expression revealed a high fibroblast-myofibroblast transition rate in arthrofibrotic fibroblasts. Fibrotic remodeling marked by enhanced XT activity, α-SMA protein expression as well as xylosyltransferase-I, collagen type III-alpha-1 and ACTA2 mRNA expression was stronger in arthrofibrotic than in control fibroblasts treated with transforming growth factor-β1 (TGF-β1). Otherwise, no differences between serum levels of XT-I activity or common fibrosis markers (galectin-3 and growth differentiation factor-15 levels (GDF-15)) were found between 95 patients with arthrofibrosis and 132 controls after TKR. In summary, XT-I was initially investigated as a key cellular mediator of arthrofibrosis and a target for therapeutic intervention. However, the blood-synovial-barrier makes arthrofibrotic molecular changes undetectable in serum. Future studies on monitoring or preventing arthrofibrotic remodeling should therefore rely on local instead of systemic parameters.