PMID- 36400339
OWN - NLM
STAT- MEDLINE
DCOM- 20230213
LR  - 20230213
IS  - 1618-0402 (Electronic)
IS  - 0940-9602 (Linking)
VI  - 246
DP  - 2023 Feb
TI  - High concentrations of Porphyromonas gingivalis-LPS downregulate Tlr4 and 
      modulate phosphorylation of ERK and AKT in murine cementoblasts.
PG  - 152023
LID - S0940-9602(22)00138-8 [pii]
LID - 10.1016/j.aanat.2022.152023 [doi]
AB  - Porphyromonas gingivalis lipopolysaccharide (PG-LPS) is an important virulence 
      factor potentially contributing to periodontal tissue destruction. Toll-like 
      receptor 4 (Tlr4) is a key mediator of NF-kB activation during pathogen 
      recognition. Previous work using Tlr4-specific antibodies demonstrated a partial 
      neutralization of PG-LPS effects on murine cementoblasts, which can affect cell 
      function and regulate gene expression of osteoclastic markers. PG-LPS also 
      potentially influence the inflammation process and the resorption of mineralized 
      tissues. Yet, such inflammatory responses and cell signaling events remain to be 
      characterized at the protein level. We thus investigated the effect of 1 and 
      10 microg/ml of PG-LPS, respectively, on cell morphology, cell viability, and 
      selected key downstream molecules of the Tlr4 signaling cascade in cementoblasts. 
      High concentrations of PG-LPS (10 microg/ml) significantly reduced cell viability 
      after 48 h. Upon PG-LPS-stimulation, Tlr4 was significantly downregulated. 
      Equally, IkappaBalpha, a downstream molecule, was downregulated in terms of 
      phosphorylation and protein production. Furthermore, downstream signaling 
      kinases, like serine/threonine kinase phospho-AKT and the mitogen-activated 
      protein kinase (MAPK)-family, specifically phospho-ERK1/2, were significantly 
      upregulated under high PG-LPS-concentrations. We provide new insights into 
      PG-LPS-triggered intracellular signaling pathways in cementoblasts and thus 
      deliver a basis for further research in PG-mediated periodontal inflammation.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Schon, Corinna Marie
AU  - Schon CM
AD  - Department of Orthodontics, Dental Clinic, RWTH Aachen University, Germany.
FAU - Craveiro, Rogerio B
AU  - Craveiro RB
AD  - Department of Orthodontics, Dental Clinic, RWTH Aachen University, Germany. 
      Electronic address: rcraveiro@ukaachen.de.
FAU - Niederau, Christian
AU  - Niederau C
AD  - Department of Orthodontics, Dental Clinic, RWTH Aachen University, Germany.
FAU - Conrads, Georg
AU  - Conrads G
AD  - Division of Oral Microbiology and Immunology, Department of Operative Dentistry, 
      Periodontology and Preventive Dentistry, University Hospital, RWTH Aachen 
      University, Germany.
FAU - Jahr, Holger
AU  - Jahr H
AD  - Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Germany; 
      Department of Orthopedic Surgery, Maastricht University Medical Center, 
      Maastricht, the Netherlands.
FAU - Pufe, Thomas
AU  - Pufe T
AD  - Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Germany.
FAU - Wolf, Michael
AU  - Wolf M
AD  - Department of Orthodontics, Dental Clinic, RWTH Aachen University, Germany.
LA  - eng
PT  - Journal Article
DEP - 20221115
PL  - Germany
TA  - Ann Anat
JT  - Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische 
      Gesellschaft
JID - 100963897
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Dental Cementum/metabolism
MH  - Inflammation
MH  - *Lipopolysaccharides/toxicity
MH  - Phosphorylation
MH  - *Porphyromonas gingivalis/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - *Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - AKT signaling
OT  - Cementoblast
OT  - MAPK signaling
OT  - OC/CM cementoblasts, remodeling
OT  - P. gingivalis-LPS
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/19 06:00
MHDA- 2023/02/07 06:00
CRDT- 2022/11/18 19:35
PHST- 2022/07/11 00:00 [received]
PHST- 2022/09/28 00:00 [revised]
PHST- 2022/11/07 00:00 [accepted]
PHST- 2022/11/19 06:00 [pubmed]
PHST- 2023/02/07 06:00 [medline]
PHST- 2022/11/18 19:35 [entrez]
AID - S0940-9602(22)00138-8 [pii]
AID - 10.1016/j.aanat.2022.152023 [doi]
PST - ppublish
SO  - Ann Anat. 2023 Feb;246:152023. doi: 10.1016/j.aanat.2022.152023. Epub 2022 Nov 
      15.