Periodontitis is an important public health problem among adults in the U.S., with major economic costs for prevention and treatment and significant impact on quality of life. Un-controlled periodontitis can cause ex- tensive tooth loss, jaw bone deterioration, and increased risk of developing systemic diseases. Conventional treatments that rely on antibiotics and mechanical removal of dental plaque are transiently effective because they indirectly address the inflammation and related immune responses that underlie periodontitis, but do not directly impact pathogenesis. Thus, there is a compelling need to investigate novel target molecules which di- rectly modulate pathogenesis for both inflammation and bone loss in periodontitis. It has been demonstrated that PPAR? agonists (PPAR?A), which is PPAR? specific, have robust protective actions limiting inflammation in autoimmune disease, modulating inflammation. Our preliminary data suggest that a PPAR?A, fenofibrate, has the potential to reduce periodontal inflammation and bone resorption in experimental periodontitis mouse mod- els, suggesting that the pathological role of PPAR? in periodontitis deserves further investigation. We propose to test the hypothesis that PPAR? not PPAR? or PPAR? plays important pathological roles in periodontitis. To that end, two distinct but complementary specific aims are proposed.
Aim1 will determine that PPAR? not PPAR? or PPAR? has expression level changes in periodontitis.
Aim 2 will determine PPAR? Knockout or overexpres- sion will affect inflammation and bone loss in experimental periodontitis mouse model. The understanding of expression level change of PPAR? in periodontitis investigated during Aim1 will provide the foundation for Aim2. The goal is to reveal the role of PPAR? in inflammatory regulation and in modulation of bone homeostasis during periodontal diseases. Building on previous experience and both Aim1 and Aim2 will lead to the development of novel, PPAR? targeted therapies for periodontits and various other oral diseases. Successful completion of this project will lead to better understanding of the molecular and cellular role of PPAR? in periodontitis, and translate this knowledge to develop an application system to achieve sustained release with noninvasive local delivery for the clinical treatment of periodontitis.

Public Health Relevance

Periodontitis is the leading cause of tooth loss, jaw bone deterioration and risk of developing systemic diseases in adults. It is necessary to investigate novel molecular targets in oral inflammation to directly treat the root cause, inflammation and related immune responses in periodontitis other than traditional treatment. The current proposal will test the hypothesis that PPAR? not PPAR? or PPAR? plays important pathological roles in periodontitis and will be extended to develop novel therapeutic strategies for periodontitis in future study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE030209-01
Application #
10108079
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Chander, Preethi
Project Start
2021-03-03
Project End
2023-02-28
Budget Start
2021-03-03
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
062190616
City
Cambridge
State
MA
Country
United States
Zip Code
02142