Distinct Effect of TCF4 on the NF kappa B Pathway in Human Primary Chondrocytes and the C20/A4 Chondrocyte Cell Line

Previous studies indicated a difference in crosstalk between canonical WNT pathway and nuclear factor-?B (NF?B) signaling in human and animal chondrocytes. To assess whether the differences found were dependent on cell types used, we tested the effect of WNT modulation on NF?B signaling in human primary articular chondrocytes in comparison with the immortalized human costal chondrocyte cell line C20/A4.We used gene expression analysis to study the effect of WNT modulation on IL1?-induced matrix metalloproteinase (MMP) expression as well as on WNT and NF?B target gene expression. In addition, we tested the involvement of RelA and TCF4 on activation of the WNT and NF?B pathway by TCF/LEF and NF?B reporter experiments, respectively.We found an inhibitory effect of both induction and inhibition of WNT signaling on IL1?-induced MMP mRNA expression in primary chondrocytes, whereas WNT modulation did not affect MMP expression in C20/A4 cells. Furthermore, TCF/LEF and NF?B reporter activation and WNT and NF?B target gene expression were regulated differentially by TCF4 and RelA in a cell type-dependent manner. Additionally, we found significantly higher mRNA and protein expression of TCF4 and RelA in C20/A4 cells in comparison with primary chondrocytes.We conclude that WNT modulation of NF?B is, at least in part, cell type dependent and that the observed differences are likely because of impaired sensitivity of the NF?B pathway in C20/A4 cells to modulations in WNT signaling. This might be caused by higher basal levels of TCF4 and RelA in C20/A4 cells compared to primary chondrocytes.