RT Journal Article SR Electronic T1 RANK-RANKL-OPG in Hemophilic Arthropathy: From Clinical and Imaging Diagnosis to Histopathology JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.120370 DO 10.3899/jrheum.120370 A1 Daniela Melchiorre A1 Anna Franca Milia A1 Silvia Linari A1 Eloisa Romano A1 Gemma Benelli A1 Mirko Manetti A1 Serena Guiducci A1 Claudia Ceccarelli A1 Massimo Innocenti A1 Christian Carulli A1 Roberto Civinini A1 Massimo Morfini A1 Marco Matucci-Cerinic A1 Lidia Ibba-Manneschi YR 2012 UL http://www.jrheum.org/content/early/2012/06/25/jrheum.120370.abstract AB Objective Hemarthrosis triggers hemophilic arthropathy, involving the target joints. The histopathogenesis of blood-induced joint damage remains unclear. The triad of receptor activator of nuclear factor- κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG; RANK-RANKL-OPG) controls bone turnover. Our aim was to evaluate RANK-RANKL-OPG expression in the synovium of hemophilic patients with severe arthropathy. Methods Synovial biopsies were obtained from 18 patients with hemophilic arthropathy and 16 with osteoarthritis (OA) who were undergoing total knee replacement and synovectomy. The severity of hemophilic arthropathy was evaluated according to ultrasonography score, the World Federation of Hemophilia (WFH) orthopedic joint scale, and the radiographic Pettersson score. RANK-RANKL-OPG expression was examined by immunohistochemistry and Western blotting. Serum levels of soluble RANKL (sRANKL) and OPG from an extended group of 67 patients with hemophilic arthropathy and 30 healthy controls were measured by ELISA. Results The mean ultrasonography, WFH orthopedic joint scale, and Pettersson scores in patients with hemophilic arthropathy indicated severe arthropathy. A decreased expression of OPG was found in hemophilic arthropathy synovium compared with patients with OA. RANK and RANKL immunopositivity was strong in the lining and sublining layers in hemophilic arthropathy synovial tissue. Western blotting confirmed the immunohistological findings. Serum levels of sRANKL and OPG in patients with hemophilia were lower than in healthy controls. Conclusion In hemophilic arthropathy, the synovium highly expressed RANK and RANKL, whereas OPG immunopositivity decreased, suggesting an osteoclastic activation. Low tissue expression of OPG paralleled the serum levels of this protein and the severity of hemophilic arthropathy assessed by ultrasonography, Pettersson, and WFH orthopedic joint scale scores.