Manicourt D H, Poilvache P, Van Egeren A, Devogelaer J P, Lenz M E, Thonar E J
Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Brussels, Belgium.
Arthritis Rheum. 2000 Feb;43(2):281-8. doi: 10.1002/1529-0131(200002)43:2<281::AID-ANR7>3.0.CO;2-7.
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.
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.
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.
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.
比较类风湿关节炎（RA）和骨关节炎（OA）患者滑液（SF）中抑瘤素M（OSM）、肿瘤坏死因子α（TNFα）和白细胞介素-6（IL-6）的水平，并确定哪些与聚集蛋白聚糖分解代谢标志物抗原性硫酸角质素（Ag KS）以及成熟胶原分子降解标志物吡啶交联物的SF水平最相关。
从RA患者（n = 31）或OA患者（n = 31）的膝关节抽取滑液。采用酶联免疫吸附测定法测量Ag KS、D-吡啶啉（D-Pyr）、吡啶啉（Pyr）、OSM、TNFα和IL-6的水平。
与OA患者相比，RA患者的OSM、TNFα、IL-6和Pyr的SF中位数水平更高，但D-Pyr的中位数水平更低。在两组中，IL-6水平与OSM和TNFα水平呈正相关。然而，OSM和TNFα水平之间的相关性仅在RA组中显著。Ag KS和Pyr水平在RA中呈正相关，而在OA中无相关性。TNFα与Ag KS之间的相关性在RA中为正，在OA中为负。此外，在RA中，OSM和IL-6水平与Pyr和Ag KS水平密切相关，但与D-Pyr水平无关，而在OA中，OSM或IL-6水平与Pyr、Ag Ks或D-Pyr水平之间无强相关性。
这项体内研究表明，TNFα和其他促炎细胞因子参与了RA中软骨聚集蛋白聚糖和胶原协同降解的上调。此外，OSM可能与其他促炎细胞因子协同作用，上调类风湿关节中软骨细胞金属蛋白酶的产生。
