RANK-RANKL-OPG in Hemophilic Arthropathy: From Clinical and Imaging Diagnosis to Histopathology

Abstract

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.

Osteoprotegerin: Multiple partners for multiple functions

“…They concluded that low tissue expression of OPG paralleled its serum levels and the severity of hemophilic arthropathy (Melchiorre et al, 2012). .These data are consistent with a randomized study showing that the prophylaxis with recombinant Factor VIII prevents joint damages in young haemophilic patients (Manco-Johnson et al 2007), possibly through a decrease in osteoclastogenesis.…”

IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy

“…33,34 An upregulation of the nuclear factor-kB pathway, which is induced by IL-1b, has been emphasized in hemophilic mice upon joint bleeding 34 and in synovial tissue of patients with hemophilic arthropathy. 35 In experimental arthritis, blocking IL-1 prevents cartilage damage upon inflammation 36,37 as is also observed in a posttraumatic osteoarthritis model. 38 Therapeutic efficacy of IL-1RA is demonstrated in hand osteoarthritis 39 and in 2 cases suffering from another form of ironinduced arthropathy in case of hemochromatosis.…”

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A

“…[7][8][9] In a previous study, we provided evidence of a strong correlation between the severity of arthropathy in HA patients and the expression of the RANK/RANKL/OPG triad in synovial tissue, as well as circulating levels of sRANKL and OPG. 19 Therefore, in the present work we investigated for the first time the possible differences in the RANK/RANKL/OPG triad between HA and HB patients.…”

“…19 Synovial samples from 16 osteoarthritis (OA) patients were included as controls. Each synovial specimen was cut into small pieces, fixed in 10% buffered formalin and, after standard processing, embedded in paraffin wax and used for light microscopy.…”

“…17 Another crucial parameter of bone biology is the molecular triad consisting of osteoprotegerin (OPG), receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), which tightly controls bone turnover and is involved in the severity of arthropathy, as demonstrated in HA. 18,19 OPG is a member of the tumor necrosis factor receptor superfamily, acts as a decoy receptor for RANKL, and competes with RANK for binding to RANKL. [20][21][22] By this mechanism, OPG down-regulates osteoclast differentiation, activity and survival both in vivo and in vitro.…”