Synovial fluid levels of tumor necrosis factor alpha and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis.
OBJECTIVE
To compare synovial fluid (SF) levels of oncostatin M (OSM), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to determine which correlate best with SF levels of antigenic keratan sulfate (Ag KS), a marker of aggrecan catabolism, and pyridinium crosslinks, markers of the degradation of mature collagen molecules.


METHODS
SF was drawn from the knee joints of patients with RA (n = 31) or OA (n = 31). Levels of Ag KS, D-pyridinoline (D-Pyr), pyridinoline (Pyr), OSM, TNFalpha, and IL-6 were measured by enzyme-linked immunosorbent assay.


RESULTS
RA patients had higher median SF levels of OSM, TNFalpha, IL-6, and Pyr, but a lower median level of D-Pyr, than OA patients. In both groups, IL-6 levels correlated positively with those of OSM and TNFalpha. However, the correlation between levels of OSM and TNFalpha was only significant in the RA group. Ag KS and Pyr levels correlated positively in RA but not in OA. The correlation between TNFalpha and Ag KS was positive in RA and negative in OA. Further, in RA, OSM and IL-6 levels correlated strongly with Pyr and Ag KS levels but not with D-Pyr levels, while there were no strong correlations in OA for OSM or IL-6 levels with Pyr, Ag Ks, or D-Pyr levels.


CONCLUSIONS
This in vivo study suggests that TNFalpha and other proinflammatory cytokines are involved in the up-regulation of the coordinated degradation of cartilage aggrecan and collagen in RA. Further, OSM may act synergistically with other proinflammatory cytokines in up-regulating the production of metalloproteinases by chondrocytes in rheumatoid joints.
Manicourt
D H
DH
Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Brussels, Belgium.
Poilvache
P
P
Van Egeren
A
A
Devogelaer
J P
JP
Lenz
M E
ME
Thonar
E J
EJ
D000328:Adult; D000368:Aged; D053674:Aggrecans; D000941:Antigens / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001673:Biodegradation, Environmental; D015415:Biomarkers / Q000032:analysis; D002356:Cartilage / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D007632:Keratan Sulfate / Q000276:immunology; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D053683:Oncostatin M; D010003:Osteoarthritis / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053674:Aggrecans; D000941:Antigens; D015415:Biomarkers; D003432:Cross-Linking Reagents; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D006131:Growth Inhibitors; D037181:Lectins, C-Type; C508351:OSM protein, human; D010455:Peptides; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D003094:Collagen; D007632:Keratan Sulfate