When dental pulp cells are exposed to the environment, whether it is due to trauma, rapidly progressing caries, or overly aggressive restoration procedures, vital pulp therapy is required to attempt to prevent the death of those cells. If this procedure fails a root canal will be required in the future. During vital pulp theray a pulp capping material is used. The objective of the pulp capping material is to stimulate the formation of a dentin bridge over the exposed pulp. Calcium hydroxide containing materials are widely used for pulp capping because of their ability to stimulate reparative dentin formation. However, calcium hydroxide has been found to be toxic to dental pulp cells. Reports of the success rate of pulp capping treatments vary greatly and it is clear that in actual dental practice current procedures are not always effective. A potential alternative, or adjunct, to calcium hydroxide compounds is the use of growth factors during pulp capping procedures. Growth factors have been shown to induce the formation of reparative dentine and we have shown that they can protect dental pulp cells against toxicity induced by a number of types of insults. Importantly, we found that the protective effects of growth factors are due to their ability to upregulate the cystine/glutamate antiporter (system xc-). System xc- mediates two important actions: the uptake of cystine and the release of glutamate. The uptake of cystine is the rate limiting step in the production of the main intracellular free radical scavenger glutathione. This finding represents a novel mechanism of growth factor effects on dental pulp cells and suggests regulation of system xc- as a key variable to explore when assessing impact of various factors on dental pulp cells. The hypothesis to be tested is that alteration in system xc- function is a determining factor in the success of pulp capping materials. The experiments of Specific Aim 1 are designed to thoroughly understand the factors that regulate system xc- in dental pulp cells and how that regulation effects their survival in cell culture. The goal of Specific Aim 2 is to determine if altered activity of system xc- determines the success of pulp capping materials. The information obtained from these studies will provide an understanding of how regulation of system xc- occurs and the consequences of that regulation. The idea being that because of the important role that system xc- plays in the maintenance of cellular glutathione levels, understanding how substances alter its expression and function should be taken into consideration whenever determining the use of materials that interact with dental pulp cells.

Public Health Relevance

When dental pulp is exposed, whether due to trauma or rapidly progressing carries, the pulp cells often die leading to either extraction or endodontic therapy. As a method of maintaining the viability of these cells we are proposing studying mechanisms by which these cells can be made resistant to toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15DE024320-01A1
Application #
8812390
Study Section
Special Emphasis Panel (ZRG1-MOSS-U (82))
Program Officer
Lumelsky, Nadya L
Project Start
2015-02-06
Project End
2018-01-31
Budget Start
2015-02-06
Budget End
2018-01-31
Support Year
1
Fiscal Year
2015
Total Cost
$453,000
Indirect Cost
$153,000
Name
Marquette University
Department
Other Basic Sciences
Type
Schools of Allied Health Profes
DUNS #
046929621
City
Milwaukee
State
WI
Country
United States
Zip Code
53233
Fahimipour, Farahnaz; Dashtimoghadam, Erfan; Rasoulianboroujeni, Morteza et al. (2018) Collagenous matrix supported by a 3D-printed scaffold for osteogenic differentiation of dental pulp cells. Dent Mater 34:209-220
Fahimipour, F; Rasoulianboroujeni, M; Dashtimoghadam, E et al. (2017) 3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering. Dent Mater 33:1205-1216