# Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $359,813

## Abstract

The periodontium is a richly innervated tissue that undergoes continuous modelling and remodeling by
alveolar bone osteoblasts, osteocytes, and osteoclasts. Studies from our laboratory have demonstrated a
close spatial relationship between trigeminal nerve ganglia and the Epithelial Rests of Malassez (ERM), an
epithelial cell network residing within the non-mineralized periodontal ligament. Inferior alveolar nerve (IAN)
transection studies resulting in dento-alveolar ankylosis and a reduction in ERM have confirmed the
essential role of sensory innervation for periodontal homeostasis. For the present application, we have
established the IAN transection model in our laboratory and provided radiographic evidence for enhanced
mineralization and ankylosis in the periodontal region of rat molars. Gene expression profiling comparing
IAN transected and control tissues demonstrated an unexpected 28-fold significant increase in galanin
(GAL) and a more than two-fold decrease in the TGF-β signaling molecules Smad2, Smad3 and Tgf-β1,
and the Wnt inhibitors Dkk1, Dkk2 and Gsk-3β. In the same IAN transection group, microRNA miR-92b
expression was more than two-fold upregulated, as verified via miRNA profiling and RT-PCR. MiR-92b
upregulation after IAN transection in conjunction with bioinformatics data implicating Wnt and Tgf-β as
possible miR-92b targets prompted us to speculate that GAL affects its skeletogenic downstream effects
through miR-92b. In vitro studies revealed that GAL treatment promoted osteogenic differentiation of PDL
progenitors and increased mineralization, while reducing osteoclastogenesis of BMMCs. Block of RhoA or
application of GAL antagonist affected PDL cytoskeletal organization and gene expression, indicating that
GAL functions through G protein coupled receptors. IWhen applied to periodontal pockets of animals
suffering from periodontitis, GAL tissue engineering constructs accomplished a 20% increase in alveolar
bone levels compared to controls, resulting in a clinically significant increase in alveolar bone height. Based
on this promising new set of data we have designed a research plan to define the role of GAL in response
to IAN transection, determine the mechanism underlying its effect on skeletogenesis, and exploit its
applicability for bone regeneration and the prevention of periodontal ankylosis. The overall goal of our
research plan is to test the hypothesis that periodontal nerves affect alveolar bone homeostasis
through a GAL–GPCR–miR-92b–TGF-β/Wnt regulatory loop and that application of GAL
neurosecretory peptides will stimulate Wnt signaling and new bone formation. We anticipate that the
outcomes of our study will lead to innovative neuropeptide based/engineering hybrid approaches that will
restore periodontal health in millions of patients and prevent the emotional and functional scars associated
with lost teeth and incomplete dentitions.

## Key facts

- **NIH application ID:** 10173750
- **Project number:** 5R01DE027930-05
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Tom Diekwisch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,813
- **Award type:** 5
- **Project period:** 2018-08-04 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173750

## Citation

> US National Institutes of Health, RePORTER application 10173750, Neurobiological control of periodontal homeostasis through microRNA, TGF-beta, and Wnt signaling (5R01DE027930-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173750. Licensed CC0.

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