Date of Award

2012

Embargo Period

8-1-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Oral Rehabilitation

College

College of Dental Medicine

First Advisor

Keith L. Kirkwood

Second Advisor

Marc Levitan

Third Advisor

Joseph E. Assad

Abstract

Introduction: Mitogen Activating Protein (MAPK) kinase phosphatase-1 (MKP-1) has been shown to be a key negative regulator of the MAP kinase pathways of the innate immune system. The impact of MKP-1 in an endodontic model has yet to be studied. Thus, the purpose of this study was to determine the role of MKP-1 in a bacterial-driven model of pathological endodontic bone loss. Methods: Pulps were exposed in both lower 1st molars of 10-week old Dusp-1+1+IMKP-1 +1+ and Dusp-1-1-IMKP-1-1- mice and left open to the oral environment for either 3 or 8 weeks. At sacrifice, mandibles were harvested and scanned by microcomputed tomography (microCT) to determine periapical bone loss. Histopathological scoring was then performed on the samples to determine the amount of inflammatory infiltrate within the periapical microenvironment. Results: Significant bone loss and inflammatory infiltrate were found in all experimental groups when compared to control. No statistical difference was found between Dusp-1+1+IMKP-1 +1+ and Dusp-1-1-IMKP-1-1- at either time point with respect to bone loss or inflammatory infiltrate. At 8 weeks, male DUSP-1-1-/MKP-1-1- mice were found to have Significantly more bone loss and inflammatory infiltrate when compared to female Dusp-1-1-IMKP-1-1- mice. There was also a significant correlation between an increase in bone loss and increase in inflammatory infiltrate. Conclusions: A sexual dimorphism exists in the periapical inflammatory process, where male Dusp-1-1-IMKP-1-1- mice have more inflammation than female Dusp-1-1-IMKP-1-1- mice. The increase in inflammatory infiltrate correlates to more bone loss in the male mice.

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