Requirement of the NF-κB pathway for induction of Wnt-5A by interleukin-1β in condylar chondrocytes of the temporomandibular joint: functional crosstalk between the Wnt-5A and NF-κB signaling pathways

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Summary

Objective

We have previously reported that interleukin-1β (IL-1β) up-regulates the expression of Wnt-5A and the activation of Wnt-5A signaling induces matrix metalloproteinase (MMP) through the c-Jun N-terminal kinase pathway in condylar chondrocytes (CCs) of the temporomandibular joint (TMJ). These results suggest that Wnt-5A could play an essential role in IL-1β-mediated cartilage destruction. The objective of this study was to investigate the molecular mechanism underlying IL-1β-induced up-regulation of Wnt-5A in TMJ CCs.

Methods

Primary CCs, limb chondrocytes (LCs) and SW1353 human chondrosarcoma cells were treated with IL-1β in the presence or absent of BAY 11-7082 (an inhibitor of IκBα-phosphorylation). Then, expression of Wnt-5A was estimated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunocytofluorescence. Transient transfection of p65 expression vector and chromatin immunoprecipitation (ChIP) assay was performed to define the effect of p65 on Wnt-5A expression.

Results

IL-1β up-regulated Wnt-5A expression at both the RNA and protein levels in articular chondrocytes. The inhibitor of IκBα-phosphorylation, BAY 11-7082, blocked the induction of Wnt-5A by IL-1β in a dose-dependent manner. Moreover, experiments with overexpression of p65 and ChIP established that induction of Wnt-5A by IL-1β is mediated through the NF-κB pathway, especially the p65 subunit.

Conclusion

These results clarify the molecular mechanism underlying up-regulation of Wnt-5A by IL-1β in chondrocytes, suggesting an important functional crosstalk between Wnt-5A and NF-κB signaling pathways. This finding provides new insights into the involvement of Wnt signaling in the cartilage destruction caused by arthritis.

Keywords

Wnt-5A
NF-κB
Interleukin-1β
Chondrocyte
Temporomandibular joint

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