# Inhibiting inflammation and bone erosion in periodontal disease by targeting cell endogenous negative signaling

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $352,688

## Abstract

The goal of this study is to understand the mechanisms underlying how cell endogenous signaling regulates
chronic inflammation and bone loss in periodontitis. Periodontitis is one of the most common inflammatory
diseases in humans that results in the destruction of periodontal tissues and alveolar bone, which ultimately
lead to teeth loss. It is estimated that majority of adults over the age of 30 suffer from periodontal bone loss.
Also, growing evidence suggests that chronic periodontal inflammation is an important risk factor for several
pathological disorders including cardiovascular disease, diabetes, atherosclerosis and arthritis. Hence, there is
an urgent need to develop novel and efficient therapeutic approaches to treat periodontal disease. Current
therapy is hindered by lack of understanding of the mechanisms underlying how cell endogenous positive and
negative signaling changes result in the reduction of periodontal tissues functional capacity and contribute to
increased incidence of periodontal disease. In our preliminary studies, we found that Gα13f/fLysM-Cre mice
exhibited severe bone loss with a significant increase in OC number, and marked periodontal ligament (PDL)
damage in periodontal disease lesions. We also found overexpression of local Gα13 constitutively active form
(Gα13CA) resulted in reduced periodontal bone loss and inflammation and repaired PDL. Importantly, we
demonstrated that Gα13 deficiency promoted nuclear factor kappa B (NF-κB) activation through
downregulated RhoA and upregulated AKT activity, and that AAV-mediated Gα13 overexpression could
effectively reduce inflammation with decreased T cells and dendritic cells. Based on our preliminary studies,
we hypothesize that Endogenous negative regulators of macrophages, dendritic cells and osteoclasts
attenuates periodontitis-induced chronic inflammation and bone loss through the Gα13/RhoA/AKT/IKK/NF-κB
pathway, and Gα13 signaling reduces the risk for periodontal disease. Three specific aims are proposed to test
our hypothesis. In Aim 1, we will determine the function of Gα13 in macrophages, dendritic cells, and OCs in
periodontal inflammation and alveolar bone loss in periodontitis by characterizing the phenotypes and
pathomechanism through loss-of-function studies. In Aim 2, we will define the function of Gα13 signaling on
periodontal inflammation and alveolar bone loss by characterizing the phenotypes and pathomechanism
through gain-of-function studies. We will dissect the molecular mechanism of the Gα13 signaling function in
regulating periodontal inflammation and tissue and bone loss in periodontitis through Gα13/RhoA/AKT/IKK/NF-
κB pathway in macrophages, dendritic cells, and OCs in Aim 3. The proposed study will provide important
insights into understand the mechanisms underlying how cell endogenous signaling regulates chronic
inflammation and bone loss in periodontitis by elucidating the underlying mechanism of Gα13 signaling.
Insights gained from this study ma...

## Key facts

- **NIH application ID:** 9897487
- **Project number:** 5R01DE023813-07
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** YI-PING LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,688
- **Award type:** 5
- **Project period:** 2014-01-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897487

## Citation

> US National Institutes of Health, RePORTER application 9897487, Inhibiting inflammation and bone erosion in periodontal disease by targeting cell endogenous negative signaling (5R01DE023813-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897487. Licensed CC0.

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