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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 Ligam...
Molecular Mechanisms of T. denticola Induced Tissue Destruction in Human Periodontal Ligament Cells

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211152719
ISBN  
9798384077794
DDC  
574
저자명  
Ganther, Sean Thomas.
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
키워드  
Extracellular matrix
키워드  
Periodontal disease
키워드  
Periodontal ligament
키워드  
Toll-like receptors
키워드  
Treponema denticola
기타저자  
University of California, San Francisco Oral and Craniofacial Sciences
기본자료저록  
Dissertations Abstracts International. 86-03B.
전자적 위치 및 접속  
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MARC

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■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.

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