# Alveolar Bone Regeneration in Diabetic Periodontitis

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2020 · $391,875

## Abstract

Over 47% of American adults aged 30 and over have periodontitis. Further, periodontitis is twice as
prevalent in diabetics as in non-diabetics, and type 2 diabetes (T2D) currently afflicts 40 million Americans.
T2D-associated periodontitis is severe and, in many cases, refractory to current treatments due to the altered
and aberrant functions of bone cells in hyperglycemic conditions. Therefore, developing an effective method to
restore and regenerate lost alveolar bone to reserve the natural teeth in diabetics is critically important.
Adiponectin, an adipokine, has anti-inflammatory and anti-diabetic properties. We have found that adiponectin
inhibits differentiation and activity of osteoclasts and significantly decreases alveolar bone loss. At the same
time, it promotes the osteoblast niche and mesenchymal stem cell migration, and enhances bone defect healing.
However, adiponectin protein-based therapy has disadvantages that limit its clinical application, including
adverse immunoreactions and the need for constant IV injection of high doses for therapeutic effect. An
adiponectin receptor agonist, AdipoRon (APR) was recently identified (Nature 503:493-9, 2013), which can be
orally administrated to ameliorate insulin resistance and glucose intolerance, and prolong the shortened
lifespan of diabetic mice. Our preliminary studies indicate that APR upregulates expression and activity of
adiponectin receptors exerting favorable effects on bone cell metabolism. Our purpose is to use APR, a small
molecule chemical compound, as a novel therapeutic agent to effectively treat diabetic periodontitis. Our
central hypothesis is that, in addition to systemically controlling hyperglycemia and inflammation, APR directly
triggers molecular signals that correct the imbalance of bone resorption and formation, reversing pathology and
promoting regeneration of lost alveolar bone, and allowing the natural teeth to be reserved. In Aim 1 we will
first determine the affinity and efficacy of APR binding to adiponectin receptors in bone cells, initiation of
downstream signal mediator expression, and enhancement of bone formation. To verify the specificity and
affinity of the interaction between this novel exogenous agonist and endogenous receptor, we will use receptor
knock out mice. In Aim 2 we will delineate the APR effect in ameliorating and correcting diabetic 'mobilopathy' -
in which cell differentiation, recruitment and migration are seriously impaired in diabetes. We will use an
adiponectin knock out mouse line to determine if APR can effectively surrogate adiponectin in promoting the
necessary microenvironment and deploying sufficient bone forming cells to regenerate alveolar bone damaged
in periodontitis. In Aim 3 we will generate experimental periodontitis in a mouse model of diabetes to further
determine the overall effects of APR in reducing hyperglycemia and inflammation as well as its anabolic effect
for periodontal bone regeneration. This translational res...

## Key facts

- **NIH application ID:** 9819687
- **Project number:** 5R01DE026507-04
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** JAKE JINKUN CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,875
- **Award type:** 5
- **Project period:** 2016-12-12 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9819687

## Citation

> US National Institutes of Health, RePORTER application 9819687, Alveolar Bone Regeneration in Diabetic Periodontitis (5R01DE026507-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9819687. Licensed CC0.

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