Date of Award

1-1-2012

Embargo Period

11-20-2024

Document Type

Thesis

Department

Stomatology

College

College of Dental Medicine

First Advisor

Keith Kirkwood

Second Advisor

Joe Krayer

Third Advisor

Renata Leite

Fourth Advisor

Viswanathan Palanisamy

Fifth Advisor

Robert Gellin

Abstract

Background: Tristetraprolin (TTP) is a key RNA-binding protein that regulates pro-inflammatory cytokines post-transcriptionally by binding to adenylate-uridylate-rich elements (AREs) within the 3'-untranslated (UTR) region. TTP is encoded by gene zfp-36. During inflammation, the p38 mitogen activated protein kinase (MAPK) pathway inactivates TTP by phosphorylation to inhibit its ability to shuttle mRNA to cytoplasmic degradation machinery. TTP knockout mice exhibit an inflammatory phenotype of arthritis, myeloid hyperplasia, and cachexia. We hypothesize that TTP directs cytokine expression in inflammatory bone loss during periodontal disease progression. Objectives: The purpose of this study is to determine if depletion of TTP affects alveolar bone loss and inflammation associated with periodontal disease progression under specific pathogen free (SPF) housing conditions. Material and Methods: We compare zfp36-/- and zfp36+/- to zfp36+/+ control mice. Sites of maxillary interradicular bone and furcation areas were used for comparison by microcomputed tomography (µCT) using bone volume fraction. Histological examination was used to quantify the degree of inflammatory infiltrate. Results: Without any inflammatory stimulation other than exposure to oral commensal bacteria, both zfp36-/- and zfp36+/- have significantly more inflammatory infiltrate and basal bone volume is quantitatively less in zfp36+/-­ and zfp36-/-mice compared to wild type controls.

Rights

All rights reserved. All rights reserved. Copyright is held by the author.

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