DKK1 exacerbates dental pulp inflammation: insights from RNA-sequencing analysis

Dickkopf-related protein 1 (DKK1) has been implicated in several inflammatory diseases; however, its role in pulpitis remains poorly understood. This study aimed to investigate the role and underlying molecular mechanisms of DKK1 on pulpitis using inflamed dental pulp cells (DPCs) as the experimental model. RNA-sequencing (RNA-seq) was conducted on varying concentrations of lipopolysaccharide (LPS)-treated DPCs. Subsequent bioinformatic analyses revealed distinct transcriptional expression patterns between moderate inflammation induced by 1 μg/ml LPS and excessive inflammation induced by 10 μg/ml LPS. Furthermore, the addition of recombinant DKK1 (200 ng/ml) to DPCs treated with 1 μg/ml LPS further enhanced the production of pro-inflammatory cytokines. Bioinformatic analyses based on RNA-seq data identified 24 hub genes in DKK1-stimulated inflamed DPCs, among which the interleukin-17 (IL-17) signaling pathway was the most significantly enriched. Correspondingly, recombinant DKK1 increased the expression of IL-17 receptor in inflamed DPCs. Taken together, these findings indicate that under moderate inflammatory conditions, DKK1 exacerbates inflammation in DPCs through enhancing the production of pro-inflammatory mediators, potentially via modulation of the IL-17 signaling pathway. Thus, targeting DKK1 might have therapeutic potential for promoting the resolution of moderate pulpitis and preventing its severe progression.