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Molecular Mechanisms of T. denticola Induced Tissue Destruction in Human Periodontal Ligament Cells
Molecular Mechanisms of T. denticola Induced Tissue Destruction in Human Periodontal Ligament Cells
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152719
- ISBN
- 9798384077794
- DDC
- 574
- 서명/저자
- Molecular Mechanisms of T. denticola Induced Tissue Destruction in Human Periodontal Ligament Cells
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 117 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: DeFranco, Anthony.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 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.
- 일반주제명
- Molecular biology
- 일반주제명
- Microbiology
- 일반주제명
- Immunology
- 일반주제명
- Dentistry
- 키워드
- Dentilisin
- 기타저자
- University of California, San Francisco Oral and Craniofacial Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798384077794
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aGanther, Sean Thomas.▼0(orcid)0000-0001-7553-155X
■24510▼aMolecular Mechanisms of T. denticola Induced Tissue Destruction in Human Periodontal Ligament Cells
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a117 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: DeFranco, Anthony.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aPeriodontal 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.
■590 ▼aSchool code: 0034.
■650 4▼aMolecular biology
■650 4▼aMicrobiology
■650 4▼aImmunology
■650 4▼aDentistry
■653 ▼aDentilisin
■653 ▼aExtracellular matrix
■653 ▼aPeriodontal disease
■653 ▼aPeriodontal ligament
■653 ▼aToll-like receptors
■653 ▼aTreponema denticola
■690 ▼a0307
■690 ▼a0410
■690 ▼a0982
■690 ▼a0567
■71020▼aUniversity of California, San Francisco▼bOral and Craniofacial Sciences.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163521▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


