The long term goal of our research is to develop a point-of-care (POC) diagnostic test to help clinicians identify sites and/or subjects that are susceptible to periodontal disease progression. The primary objective of this project is to identify biomarkers of periodontal disease progression. The central hypothesis is that a combination of host analytes and subgingival species will be effective as biomarkers of periodontal disease progression. Periodontal diseases are the most common cause of tooth loss among adults in the United States and recent studies suggested that they increase the risk for systemic conditions such as cardiovascular diseases, diabetes, respiratory diseases and can affect reproductive outcome. Further, periodontal diseases progress through "bursts" of activity followed by periods of quiescence. Early accurate identification of individuals and/or sites that are undergoing active disease progression is critical to signal the need for immediate intervention to minimize tooth loss, allow for proper allocation of resources to treat susceptible individuals, and limit the potential systemic sequelae of these infections. However, there are no practical clinical means of identifying periodontal sites and/or subjects that are progressing. Better biomarkers of periodontal disease activity are urgently needed to improve periodontal disease diagnosis, guide therapy, monitor activity, and evaluate treatment response.
Aim 1 will examine the longitudinal variability of levels of host biomarkers in GCF and saliva.
Aim 2 will examine the diagnostic utility of GCF and salivary levels of host biomarkers and uncultivated and cultivable taxa in saliva and in subgingival biofilm samples for discriminating progressing and non-progressing periodontal sites and subjects.
Aim 3 will determine the effects of periodontal therapy on the levels of salivary and GCF biomarkers and on uncultivated and cultivable taxa in saliva and in subgingival biofilms. Factors that strengthen this proposal include: 1) participation by two NIH Clinical and Translational Science Award centers (The Forsyth Institute and Michigan Center for Oral Health Research);2) vast experience of both Centers in multiplex quantification of host biomarkers in oral fluids;3) access to the newly developed RNA-oligonucleotide quantification technique (ROQT) for quantifying uncultivated and cultivable bacterial taxa;and 4) access to state-of-the-art bioinformatics cores to support analysis of large data sets. This project addresses the NIDCR's strategic interest in "early detection and identification of risk factors for periodontal disease" and reaffirms the center's commitment to "facilitate the translation of science into clinical practice". Successful completion of this project will lead to validation of biomarkers that can be used in POC tests to help clinicians identify sites and subjects at risk for disease progression who require immediate intervention.

Public Health Relevance

Despite advances in our knowledge of the causes and risk factors associated with periodontitis, there are no signs of a decline in periodontal disease prevalence. In fact, longer retention of teeth, coupled with an aging population might account for future increases in the number of subjects affected by tooth loss due to periodontal destruction. The total expenditure on treating and preventing periodontal diseases is estimated in billions of dollars. At present there are no practical clinical means of establishing which periodontal sites or subjects are active. The discovery of biomarkers of periodontal disease progression would provide clinicians with important information regarding the need for treatment, evaluation of treatment outcomes and prognosis for patients that could help improve preventive and therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DE021127-04S1
Application #
8914088
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Atkinson, Jane C
Project Start
2010-09-27
Project End
2015-05-31
Budget Start
2014-08-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$2,000,000
Indirect Cost
$880,322
Name
Forsyth Institute
Department
Type
DUNS #
062190616
City
Cambridge
State
MA
Country
United States
Zip Code
02142
de Lima Oliveira, Ana Paula; de Faveri, Marcelo; Gursky, Lauren Christine et al. (2012) Effects of periodontal therapy on GCF cytokines in generalized aggressive periodontitis subjects. J Clin Periodontol 39:295-302
Teles, F R; Teles, R P; Uzel, N G et al. (2012) Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodontal Res 47:95-104
Teles, R; Wang, C-Y (2011) Mechanisms involved in the association between periodontal diseases and cardiovascular disease. Oral Dis 17:450-61