Wnt5a Regulates Odontoblast Inflammation by Promoting CCL2 Expression

Abstract

Objective Wnt5a is involved inflammation, including pulpitis, by upregulating cytokine/chemokine expression. Odontoblasts are the first layer cells in dental pulp and respond to inflammatory stimuli. However, whether Wnt5a is involved in odontoblast inflammation is unclear. This study aimed to investigate the role of Wnt5a in odontoblast inflammation. Methods We measured and compared Wnt5a- or TNF-α-induced cytokine/chemokine expression in mouse odontoblast-like (17IIA11) cells by real-time PCR and Western blotting. Transwell assays were used to examine the effect of Wnt5a on RAW264.7 macrophage migration. We examined whether the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were involved in the molecular mechanism of TNF-α or Wnt5a in 17IIA11 cells by Western blotting. Results TNF-α upregulated Wnt5a in odontoblasts. Wnt5a upregulated CCL2 expression in odontoblasts and enhanced RAW264.7 cell migration. We also found that TNF-α-induced Wnt5a expression was abrogated by inhibiting the MAPK pathway or NF-κB activity and that inhibiting MAPK activity could lead to decreased NF-κB activity. Conclusions Wnt5a is involved in the TNF-α-induced inflammatory response in odontoblasts. TNF-α upregulates Wnt5a expression via MAPK-dependent NF-κB activation in odontoblasts. Wnt5a upregulates CCL2 expression in odontoblasts and enhances RAW264.7 macrophage migration.