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RANK-RANKL-OPG in Hemophilic Arthropathy: From Clinical and Imaging Diagnosis to Histopathology.
MedLine Citation:
PMID:  22753650     Owner:  NLM     Status:  Publisher    
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.
Daniela Melchiorre; Anna Franca Milia; Silvia Linari; Eloisa Romano; Gemma Benelli; Mirko Manetti; Serena Guiducci; Claudia Ceccarelli; Massimo Innocenti; Christian Carulli; Roberto Civinini; Massimo Morfini; Marco Matucci-Cerinic; Lidia Ibba-Manneschi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-1
Journal Detail:
Title:  The Journal of rheumatology     Volume:  -     ISSN:  0315-162X     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
From the Department of Biomedicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi (AOUC); the Excellence Centre for Research, Transfer and High Education DENOthe; the Department of Anatomy, Histology and Forensic Medicine; the Regional Reference Center for Inherited Coagulopathies, AOUC; and the Department of Traumatology and Orthopedics, University of Florence, Florence, Italy.
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