title: Human xylosyltransferases--mediators of arthrofibrosis? New pathomechanistic insights into arthrofibrotic remodeling after knee replacement therapy.
abstract: 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.
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Faust
authors.affiliation: Klinik am Rosengarten, Bad Oeynhausen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Traut
authors.affiliation: Klinik am Rosengarten, Bad Oeynhausen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Nolting
authors.affiliation: Orthopaedicum Hannover, Zentrum für orthopädische Chirurgie, Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Petschallies
authors.affiliation: Justus-Liebig Universität Gießen, Internal Medicine and Rheumatology, Kerckhoff-Klinik Bad Nauheim, Bad Nauheim, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
authors.affiliation: Universitätsklinikum Jena, Rudolf-Elle Waldkrankenhaus Eisenberg, Eisenberg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Kunisch
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kuhn
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hendig
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D016022:Case-Control Studies; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D037502:Galectin 3 / Q000097:blood; D005786:Gene Expression Regulation; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D007592:Joint Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D010430:Pentosyltransferases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016059:Range of Motion, Articular; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D000199:Actins; D037502:Galectin 3; D055436:Growth Differentiation Factor 15; D010430:Pentosyltransferases; D053773:Transforming Growth Factor beta1; D000097608:UDP Xylose-Protein Xylosyltransferase; C541116:ACTA2 protein, human