microRNA-200c Mitigates Pulpitis and Promotes Dentin Regeneration

<i>MicroRNA (miR)-200c</i> enhances osteogenesis, modulates inflammation, and participates in dentin development. This study was to investigate the beneficial potential of <i>miR-200c</i> in vital pulp therapy (VPT) by mitigating pulpitis and promoting dentin regeneration. We explored the <i>miR-200c</i> variations in inflamed pulp tissues from patients with symptomatic irreversible pulpitis and primary human dental pulp-derived cells (DPCs) challenged with <i>P.g.</i> lipopolysaccharide (<i>Pg</i>-LPS). We further assessed the functions of overexpression of <i>miR-200c</i> on odontogenic differentiation, pulpal inflammation, and dentin regeneration in vitro and in vivo. Our findings revealed a noteworthy downregulation of <i>miR-200c</i> expression in inflamed pulp tissues and primary human DPCs. Through the overexpression of <i>miR-200c</i> via transfecting plasmid DNA (pDNA), we observed a substantial downregulation of proinflammatory cytokines interleukin (IL)-6 and IL-8 in human DPCs. Furthermore, this overexpression significantly enhanced the transcript and protein levels of odontogenic differentiation markers, including Runt-related transcription factor (Runx)2, osteocalcin (OCN), dentin matrix protein (DMP)1, and dentin sialophosphoprotein (DSPP). In a rat model of pulpitis induced by <i>Pg</i>-LPS, we demonstrated notable benefits by local application of pDNA encoding <i>miR-200c</i> delivered by CaCO₃-based nanoparticles to reduce pulpal inflammation and promote dentin formation. These results underscore the significant impact of locally applied <i>miR-200c</i> in modulating pulpal inflammation and facilitating dentin repair, showcasing its ability to improve VPT outcomes.