Objective: Articular cartilage is the main target for tumor necrosis factor-alpha (TNF-alpha) and interleukin 1(IL-1) actions. These cytokines are believed to mediate cartilage degradation in arthritis. We studied the expression of TNF receptors (TNF-R) on human articular chondrocytes and their regulation by IL-1beta, TNF-alpha, and basic fibroblast growth factor (bFGF).
Methods: The expression of TNF-R55 and TNF-R75 on human nonarthritic articular chondrocytes was analyzed on protein and mRNA levels by ligand binding studies and reverse transcription polymerase chain reaction (RT-PCR) technique. The regulation of these receptors induced by IL-1 TNF-alpha, and bFGF on mRNA level was studied using RT-PCR.
Results: Both TNF-R55 and TNF-R75 are expressed constitutively on human articular chondrocytes, and the number of both receptors varied between 822 and 3880 receptors per cell, depending on the donor cartilage used. Using TNF receptor-specific antibodies, we show that normal chondrocytes express mainly TNF-R55. These results are consistent with the mRNA data obtained by RT-PCR. mRNA expression of TNF receptors is regulated by IL-1beta, TNF-alpha, and bFGF. On human chondrocytes the expression of TNF-R75 mRNA was markedly upregulated by IL-ID, TNF-alpha, and bFGF, whereas the expression of TNF-R55 mRNA remained largely unchanged. A combination of IL-1beta and TNF-alpha, but not of IL-1beta and bFGF, showed an additive effect on TNF-R75 mRNA expression.
Conclusion: The expression of TNF-R55 and TNF-R75 on human articular chondrocytes is modulated independently by IL-1beta, TNF-alpha, and bFGF, suggesting a role of these regulatory mechanisms in the degradation processes of human articular cartilage in inflammatory joint diseases.