科研之友
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摘要
Objective: Previous studies indicated a difference in crosstalk between canonical WNT pathway and nuclear factor-kappa B (NF kappa 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 kappa B signaling in human primary articular chondrocytes in comparison with the immortalized human costal chondrocyte cell line C20/A4. Design: We used gene expression analysis to study the effect of WNT modulation on IL1 beta-induced matrix metalloproteinase (MMP) expression as well as on WNT and NF kappa B target gene expression. In addition, we tested the involvement of RelA and TCF4 on activation of the WNT and NF kappa B pathway by TCF/LEF and NF kappa B reporter experiments, respectively. Results: We found an inhibitory effect of both induction and inhibition of WNT signaling on IL1 beta-induced MMP mRNA expression in primary chondrocytes, whereas WNT modulation did not affect MMP expression in C20/A4 cells. Furthermore, TCF/LEF and NF kappa B reporter activation and WNT and NF kappa 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. Conclusions: We conclude that WNT modulation of NF kappa B is, at least in part, cell type dependent and that the observed differences are likely because of impaired sensitivity of the NF kappa 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.
- 出版日期2014-7
