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Pathophysiology of Hemophilic Arthropathy - PubMed

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Pathophysiology of Hemophilic Arthropathy

Daniela Melchiorre et al. J Clin Med. 2017.

Abstract

Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin-OPG; receptor activator of nuclear factor κB-RANK; RANK ligand-RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.

Keywords: hemarthrosis; hemophilia; hemophilic arthropathy; synovitis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Schematic representation of the mechanisms of blood-induced joint damage in hemophilia. The role of iron (Fe2+) interacting with hydrogen peroxide (H2O2), activation of macrophages (Mo/Mφ), matrix metalloproteinases (MMPs), and pro-inflammatory cytokines is highlighted. Adapted with permission from [17]. IL: interleukin; RBC: red blood cell.

Figure 2
Figure 2

Photomicrographs showing the expression of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in synovial tissue from patients with hemophilia A, hemophilia B, and osteoarthritis. Representative photomicrographs of tissue sections subjected to immunoperoxidase staining for RANK, RANKL, and OPG (brownish-red color) and counterstained with hematoxylin are shown. Arrows indicate OPG immunostaining in the synovial lining layer. Original magnification: ×20. Scale bar: 100 µm. Reproduced with permission from [46].

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