Evidence map›Paper›PMID 24973519›Full record

ArticleArchives of oral biology2014

Treponema denticola upregulates MMP-2 activation in periodontal ligament cells: interplay between epigenetics and periodontal infection.

Di Miao, Valentina Godovikova, Xu Qian, Suchithra Seshadrinathan, Yvonne L Kapila, J Christopher Fenno

Open access · greenAbstract read
In one paragraph

Article in Archives of oral biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 33 citations in OpenAlex.

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  10. Frontiers in cellular and infection microbiology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Di MiaoDepartment of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
Valentina GodovikovaDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
Xu QianDepartment of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
Suchithra SeshadrinathanDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
Yvonne L KapilaDepartment of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
J Christopher FennoDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United States. Electronic address: fenno@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Apoptosis Regulated by Fibronectin Signaling PathwaysR01DE013725 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAPILA, YVONNE L · 2001 to 2010
$2.8M
Surface protein complexes of oral treponemes: assembly and host cell interactionsR01DE018221 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FENNO, J CHRISTOPHER · 2009 to 2010
$752k
NIDCR NIH HHS DE013725NIDCR NIH HHS DE018221NIDCR NIH HHS R01 DE013725NIDCR NIH HHS R01 DE018221
6 · The paper itself

Abstract

objectivePeriodontal pathogens initiate chronic dysregulation of inflammation and tissue homeostasis that characterize periodontal disease. To better understand oral microbe-host tissue interactions, we investigated expression and activation of MMP-2 in periodontal ligament cells following Treponema denticola challenge.

designCultured PDL cells were challenged with T. denticola, and bacterial adherence, internalization and survival were assayed by immunofluorescence microscopy and antibiotic protection assays, respectively. MMP-2 activation was detected by zymography. MMP-2, MT1/MMP and TIMP-2 expression following T. denticola challenge was determined by qRT-PCR. Promoter methylation of MMP-2 and MT1/MMP was screened by methylation-sensitive restriction analysis and by bisulfite DNA sequencing.

resultsT. denticola adhered to and was internalized by PDL cells but did not survive intracellularly beyond 24h. Importantly, while dentilisin activity in PDL culture supernatants gradually decreased following T. denticola challenge, MMP-2 activation persisted for up to 5 days, suggesting involvement of other regulatory mechanisms. Transcription and expression of MT1/MMP and TIMP-2 increased in response to T. denticola challenge. However, consistent with previously reported constitutive pro-MMP-2 expression in PDL cells, the MMP-2 promoter was hypomethylated, independent of T. denticola challenge.

conclusionsMMP-2 promoter hypomethylation is consistent with constitutive pro-MMP-2 expression in PDL cells. This, coupled with T. denticola-mediated upregulation of MMP-2-related genes and chronic activation of pro-MMP-2, mimics key in vivo mechanisms of periodontal disease chronicity, in particular MMP-2-dependent matrix degradation and bone resorption. Adherence and/or internalization of T. denticola may contribute to these processes by one or more regulatory mechanisms, including contact-dependent signal transduction or other epigenetic mechanisms.

Indexed as

Blotting, WesternCells, CulturedDNA MethylationEpigenesis, GeneticHumansMatrix Metalloproteinase 2Microscopy, FluorescencePeriodontal LigamentPeriodontitisTissue Inhibitor of Metalloproteinase-2Transcriptional ActivationTreponema denticolaUp-RegulationMatrix Metalloproteinase 2MMP2 protein, humanTIMP2 protein, humanTissue Inhibitor of Metalloproteinase-2EpigeneticsMMP-2MT1/MMPProteasesTIMP-2Treponema

Identifiers

PMID24973519
PMCPMC4120104
OpenAlexW2161654641

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.