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A Clue To Rheumatoid Arthritis In Osteoprotegerin Expression?

A deficiency in osteoprotegerin (OPG) expression in the inflamed joint of rheumatoid arthritis patients with synovitis may be important in the development of radiologically defined joint erosions.

This is the suggestion of an analysis of synovial tissue OPG expression in patients with rheumatoid arthritis (RA), spondyloarthropathies and osteoarthritis and in normal control subjects.

In contrast to spondyloarthropathy patients with active synovitis, patients with RA and active synovitis have deficient OPG expression on both macrophage type synovial lining cells and endothelial cells, reports this multicentre study from Australia and the Netherlands.

Led by Dr D R Haynes from the University of Adelaide, Adelaide, the investigators sought to demonstrate, in RA patients, the expression of OPG and receptor activator of nuclear factor kappaB ligand (RANKL) in synovial tissue. They also wanted to establish the cell lineage expressing OPG and compare the OPG expression in RA, spondyloarthropathies, osteoarthritis and normal synovial tissue.

Synovial biopsy specimens were obtained by arthroscopy from 16 RA and 12 spondyloarthropathy patients with active synovitis of a knee joint, six RA patients with no evidence of active synovitis, 10 patients with osteoarthritis and 18 normal subjects.

Immunohistological analysis was done using monoclonal antibodies (mAb) to detect OPG and RANKL expression, and dual immunohistochemical evaluation was done with lineage-specific monoclonal antibodies (macrophages, fibroblasts and endothelial cells) and OPG. This was to determine the cell lineages expressing OPG.

Sections were evaluated by computer-assisted image analysis and semiquantitative analysis.

Two patterns of OPG expression emerged, one exclusively in endothelial cells and one expressed predominantly in macrophages in the synovial lining layer. Both patterns of OPG staining could be blocked with excess recombinant OPG.

In all synovial tissues except those from patients with active RA, there was endothelial and synovial lining OPG expression.

In contrast to this, RANKL expression was seen predominantly in synovial tissue from patients with active disease, mainly in sublining regions, particularly within areas of lymphocyte infiltration.
Rheumatology (Oxford) 2003 Jan;42(1):123-134. "Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls."

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