Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls.
OBJECTIVE
To demonstrate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in synovial tissue from rheumatoid arthritis (RA) patients, establish the cell lineage expressing OPG and compare the expression of OPG in RA, spondyloarthropathies, osteoarthritis and normal synovial tissue.


METHODS
Synovial biopsy specimens were obtained at 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 performed using monoclonal antibodies (mAb) to detect OPG and RANKL expression. In addition, dual immunohistochemical evaluation was performed with lineage-specific monoclonal antibodies (macrophages, fibroblasts and endothelial cells) and OPG to determine the cell lineages expressing OPG. The sections were evaluated by computer-assisted image analysis and semiquantitative analysis.


RESULTS
Two patterns of OPG expression were seen, 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. Endothelial and synovial lining expression of OPG was seen in all synovial tissues except those from patients with active RA. In contrast, RANKL expression was seen predominantly in synovial tissue from patients with active disease, mainly in sublining regions, particularly within areas of lymphocyte infiltration.


CONCLUSIONS
OPG expression on macrophage type synovial lining cells as well as endothelial cells is deficient in RA patients with active synovitis, in contrast to that seen in spondyloarthropathy patients with active synovitis. This deficiency in OPG expression in the inflamed joint of RA patients may be important in the development of radiologically defined joint erosions.
Haynes
D R
DR
Department of Pathology, University of Adelaide, Repatriation General Hospital, Daws Road, Daw Park, South Australia 5041, Australia.
Barg
E
E
Crotti
T N
TN
Holding
C
C
Weedon
H
H
Atkins
G J
GJ
Zannetino
A
A
Ahern
M J
MJ
Coleman
M
M
Roberts-Thomson
P J
PJ
Kraan
M
M
Tak
P P
PP
Smith
M D
MD
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000378:metabolism* / Q000601:surgery; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000601:surgery; D001182:Arthroscopy; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis; D016022:Case-Control Studies; D004727:Endothelium / Q000737:chemistry; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D007719:Knee Joint; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000601:surgery; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor; D025242:Spondylarthropathies / Q000378:metabolism / Q000601:surgery; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000737:chemistry*
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human