# Pulpitis Transiently Affect Hepatic Bone Morphogenetic Protein 9 Expression by Lipopolysaccharide

## TL;DR

This study shows that pulpitis can temporarily affect liver BMP9 levels through LPS, suggesting a link between oral and systemic health.

## Contribution

The novel finding is that pulpitis-induced LPS transiently affects BMP9 expression via H3K9 dimethylation and G9a activity.

## Key findings

- BMP9 expression in the liver and blood initially decreases then increases in pulpitis models.
- LPS stimulation of hepatic stellate cells mirrors BMP9 trends seen in vivo.
- UNC0642 treatment restores BMP9 levels by inhibiting G9a methyltransferase activity.

## Abstract

The connection between oral and systemic diseases is receiving increasing attention. Pulpitis is an infectious disease, and its potential impact on the systemic system deserves further investigation.

A rat/mouse pulpitis model was utilized to explore the variations in bone morphogenetic protein 9 (BMP9) and lipopolysaccharide (LPS) concentrations within liver tissue and blood. Hepatic stellate cells were cultivated and subsequently stimulated with LPS. Histone H3K9 methylation and associated methyltransferase levels were quantified. G9a function was investigated by the G9a methyltransferase inhibitor UNC0642.

In rats and mice with pulpitis, BMP9 expression initially declined in both the liver and blood, followed by a subsequent increase. This BMP9 trend in LPS-stimulated hepatic stellate cells mirrored the findings observed in vivo. Mechanistically, the involvement of H3K9 dimethylation and G9a methyltransferase in this process was elucidated. Treatment with UNC0642 successfully restored suppressed BMP9 levels. Chromatin immunoprecipitation assays further confirmed an increased enrichment of H3K9 dimethylation in the promoter region of the BMP9 gene following LPS stimulation of mouse hepatic stellate cells.

These findings suggested that LPS in pulpitis might transiently influence the expression of BMP9 in liver tissues, and pulpitis might have potential effects on systemic tissues and organs.

This study provides a proof-of-concept for targeting epigenetic pathways to mitigate the oral-systemic disease link, motivating future clinical trials in high-risk populations.