자료유형  

 학위논문

Control Number  

0017163521

International Standard Book Number  

9798384077794

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Ganther, Sean Thomas.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, San Francisco., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

117 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

General Note  

Advisor: DeFranco, Anthony.

Dissertation Note  

Thesis (Ph.D.)--University of California, San Francisco, 2024.

Summary, Etc.  

요약Periodontal disease (PD) is a complex infection driven by a myriad of bacterial species interacting with host tissues, triggering the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling enzymes like Matrix Metalloproteinases (MMP), culminating in periodontal tissue degradation. Despite clinical intervention, severe periodontitis patients exhibit a persistent pro-inflammatory state, perpetuating tissue destruction. Treponema denticola (T. denticola), an oral anaerobic bacteria, notably abundant in advanced lesions, harbors potent and abundantly expressed virulence factors, including the chymotrypsin-like protease complex (CTLP or dentilisin), implicated in various pathogenic activities like adhesion, ECM degradation, and MMP activation. Our research has shown elevated T. denticola DNA levels correlated with increased MMP2 mRNA expression. Short-term exposure of human periodontal ligament fibroblast cells (hPDL) to wild-type T. denticola bacteria led to prolonged upregulation of the MMP-2-MMP-14-TIMP-2 activation axis for up to 12 days in Vitro. Despite extensive protein-level studies, direct links between T. denticola protease activity and periodontal tissue destruction at transcriptional or epigenetic levels remain scarce. Chemically characterized as a tri-acylated lipoprotein, dentilisin more than likely engages with TLR2-dependent mechanisms. Thus, based on literature and current data from our laboratory, we hypothesize that T. denticola exploits dentilisin to activate a TLR2-dependent pathway, inducing the upregulation of tissue-destructive genes in hPDL cells. This work sheds light on the specific interactions between human periodontal ligament cells and T. denticola, elucidating the transcriptional drivers of periodontal disease chronicity using an array of molecular techniques and high-throughput sequencing methods, revealing potential therapeutic targets beyond antibiotics.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Dentistry.

Index Term-Uncontrolled  

Dentilisin

Index Term-Uncontrolled  

Extracellular matrix

Index Term-Uncontrolled  

Periodontal disease

Index Term-Uncontrolled  

Periodontal ligament

Index Term-Uncontrolled  

Toll-like receptors

Index Term-Uncontrolled  

Treponema denticola

Added Entry-Corporate Name  

University of California, San Francisco Oral and Craniofacial Sciences

Host Item Entry  

Dissertations Abstracts International. 86-03B.

Electronic Location and Access  

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Control Number  

joongbu:658535