# Histone acetylation facilitates multidirectional pulp repair through Neuregulin-1 mobilization

## TL;DR

Enhancing histone acetylation helps repair dental pulp by boosting NRG1, which reduces inflammation and promotes tissue regeneration.

## Contribution

The study shows that histone acetylation modulates NRG1 to improve pulp repair with anti-inflammatory and regenerative effects.

## Key findings

- NRG1 overexpression reduces inflammation and promotes dentin and nerve regeneration.
- HDAC inhibitors like SAHA enhance histone acetylation and NRG1 activation for pulp repair.
- H3K9 and H3K27 acetylation levels correlate with NRG1 expression during pulp repair.

## Abstract

Appropriate dental pulp repair is based on effective control of inflammation and involves the regeneration of dental pulp nerves, blood vessels (soft tissue), and dentin (hard tissue). Limited evidence has shown how to modulate the uncertainty due to individual variability in dental pulp repair. NRG1, a cytokine modulating nerve injury and repair, was intricately associated with the outcome of pulp repair. Yet, its mobilization in spontaneous pulp repair had individual variability. The study further explored the role of NRG1 during pulp repair as well as an epigenetic way to modulate NRG1 through histone acetylation to enhance pulp repair. Overexpression of NRG1 exhibited the effects of anti-inflammation and integrated regeneration of soft and hard tissue, by inhibiting pro-inflammatory factors IL-1β, IL-8, and promoting the expressions of DSPP, DMP1 (dentin regeneration), and nestin (nerve regeneration). Moreover, restricted H3K9 and H3K27 acetylation correlated with NRG1 expression in pulp repair both temporally and spatially, showing individual variability as well. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, enhanced H3K9ac and H3K27ac, which dramatically activated NRG1, suppressed pulp inflammation, and facilitated soft and hard tissue regeneration. In summary, targeting histone acetylation with HDAC inhibitors may be an effective approach to promote pulp repair by activating NRG1.

Enhanced histone acetylation facilitated pulp repair through NRG1 mobilization via anti-inflammatory and pro-regenerative mechanisms. NRG1 driven by enhanced histone acetylation, started the journey of dental pulp repair. NRG1 promoted pulp regeneration by inhibiting proinflammatory factors and enhanced dentin and nerve regenerative capacity.

Enhanced histone acetylation facilitated pulp repair through NRG1 mobilization via anti-inflammatory and pro-regenerative mechanisms. NRG1 driven by enhanced histone acetylation, started the journey of dental pulp repair. NRG1 promoted pulp regeneration by inhibiting proinflammatory factors and enhanced dentin and nerve regenerative capacity.