Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Metabolic-Purinergic fitness in periodontal health and disease

Award Number: R01DE033982
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2030

Group Awards By:

View Award Description

Metabolic-Purinergic fitness in periodontal health and disease - Project Summary Despite periodontitis typically manifesting in later stages of life, our understanding of the mediators and biomarkers linked to severe disease manifestation and hyper-inflammatory responses leading to osteolytic destruction remains limited. In this context, the role of nucleotide-metabolizing enzymes, such as ecto-5’- nucleotidase (NT5E), or CD73, in characterizing purinergic influence on inflammatory alveolar bone loss remains largely unexplored. During the inflammatory process, there is an increase in extracellular ATP (eATP), and CD73 serves as the final step in converting eATP to adenosine (ADO) aiming to restore homeostasis. Our recent findings have illuminated the critical role of CD73-dependent ADO in controlling inflammation-associated state in gingival fibroblasts, implicating mitochondrial metabolism as a central mechanism in the pathogenesis of hyper-inflammatory gingival responses. Furthermore, our research has revealed that CD73-/- mice exhibit more aggressive alveolar bone loss in a ligature-induced periodontitis model. We observed a heightened proinflammatory state in murine primary gingival fibroblasts and a more aggressive osteoclast phenotype in mice lacking CD73 due to their increased mitochondrial activity. Our strong preliminary data have led us to hypothesize that ectonucleotidase CD73 in fibroblasts directs the metabolic capabilities of a stromal-osteoclast axis, due to increased migration and retention of osteoclast precursors leading to excessive bone resorption in periodontal pathogenesis. This hypothesis will be investigated through two Specific Aims: Specific aim 1 will delineate how CD73 deficiency leads to metabolic dysfunctional inflammation-associated gingival fibroblast state and define the link to osteoclast hyper-function. Since mitochondrial dysfunction is one of the hallmarks of ageing, age is incorporated as a biological variable. Specific aim 2 will study whether metabolic dysfunction drives an imbalance in the purinergic fitness and energy metabolism influencing a stromal-osteoclast axis in periodontium. Sex- related differences in metabolism of males and females will be considered. This research will lead to a comprehensive understanding of CD73 function in the periodontium as well as improve our knowledge of purinergic-metabolic relationship in periodontal health and disease. It will enable us to determine whether CD73 ectonucleotidase can be specifically targeted to manage periodontal homeostasis serving as a potential candidate for early diagnosis to prevent hyper-inflammatory responses.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $389,404 )
2026	2026	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	2	3/30/2026	NON-COMPETING CONTINUATION	$389,404
														Subtotal = $389,404

Issue Date FY: 2025 ( Subtotal = $381,216 )
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	000	1	5/23/2025	NEW	$381,216
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Oral Diseases and Disorders Research	001	1	7/2/2025	NEW	$0
														Subtotal = $381,216

Grand Total All Awards = $770,620

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metabolic-Purinergic fitness in periodontal health and disease

Award Number: R01DE033982

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer