# Epigenetic Regulation of Periodontal Inflammation

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $380,899

## Abstract

PROJECT SUMMARY/ABSTRACT
 Periodontitis is initiated by a dysbiotic microbial community; however, it is the host immune response to the
microbial insults that ultimately causes the damage to the tooth supporting complex. There are considerable
limitations to the current standard of care for treatment of periodontal diseases, which is focused on eliminating
the biofilms. Increasing evidence indicates that the susceptibility to periodontitis is largely determined by the host
response. Therapies targeting the uncontrolled, overly aggressive inflammation are critical not only for blocking
the diseases but also for the reconstruction of a healthy periodontal ecosystem. Epigenetic regulation such as
histone acetylation is essential for inflammatory gene expression. A specific histone acetylation pattern is
proposed in inflammatory diseases including periodontitis. Bromodomain and extraterminal domain (BET)
proteins are the “reader” that mediate the epigenetic marks to the transcription machinery. BET inhibitors are an
emerging class of epigenetic drugs for inflammatory diseases. Recently, we found that RVX-208, a selective
BET inhibitor that is being tested in a Phase 3 clinical trial for cardiovascular diseases, significantly suppresses
inflammatory cytokine production and inhibits osteoclast differentiation. These findings suggested that histone
acetylation and BET proteins may have important roles in periodontal inflammation, and may be potential
diagnostic markers and pharmaceutical targets for periodontitis. To better understand epigenetic regulation in
periodontitis and develop a novel therapeutic for periodontitis, we propose to 1) Identify the histone acetylation
and BET protein expression profile in periodontitis patients; 2) Define the role of BET proteins in periodontal
inflammation; 3) Determine if targeting histone acetylation by a selective BET inhibitor can ameliorate periodontal
inflammation and alveolar bone loss in vivo. The proposed studies will generate critical clinical data to support
the importance of epigenetic regulation in the pathogenesis of periodontal disease and help us develop the first
“epi” drug to treat the diseases.
1

## Key facts

- **NIH application ID:** 10088436
- **Project number:** 5R01DE028915-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Zhao Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,899
- **Award type:** 5
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088436

## Citation

> US National Institutes of Health, RePORTER application 10088436, Epigenetic Regulation of Periodontal Inflammation (5R01DE028915-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10088436. Licensed CC0.

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