Evidence map›Paper›PMID 29621430›Full record

ArticleJournal of dental research2018

17β-estradiol Induces MMP-9 and MMP-13 in TMJ Fibrochondrocytes via Estrogen Receptor α.

N Ahmad, S Chen, W Wang, S Kapila

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of dental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
1.0field-weighted citation impact, top 28% 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

22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
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  18. Drivers and suppressors of triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. TMD in Females with Menstrual Disorders.International journal of environmental research and public health · 2021
    Article
  20. Review
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

4 authors at 3 institutions in 1 country.

N Ahmad1 Biology Department, Henry Ford College, Dearborn, MI, USA.
S Chen3 Division of Orthodontics, Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.
W Wang4 Private Practice, Ann Arbor, MI, USA.
S Kapila3 Division of Orthodontics, Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.
University of California, San Francisco · USAnn Arbor Center for Independent Living · USHenry Ford College · US

Funding

Hormone-Receptor-MMP Axis in Degenerative TMJ DiseasesR01DE018455 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAPILA, SUNIL D · 2007 to 2011
$1.8M
NIDCR NIH HHS R01 DE018455
6 · The paper itself

Abstract

Temporomandibular joint (TMJ) disorders, including degenerative TMJ disease, occur primarily in women of reproductive age. Previous studies showed elevated estrogen levels in subjects with TMJ disorders relative to controls and the presence of estrogen receptors α and β (ERα and ERβ) in TMJ fibrocartilage. Additionally, estrogen-induced overexpression of specific matrix metalloproteinases (MMPs), including MMP-9 and MMP-13, in TMJ fibrocartilage is accompanied by loss of extracellular matrices. However, the contribution of ERα and ERβ in estrogen-mediated induction of MMP-9 and MMP-13 and the signaling cascade leading to the upregulation of these MMPs have not been elucidated. Here, we show that specific siRNAs and selective ER antagonists effectively block ERα or ERβ expression in primary mouse TMJ fibrochondrocytes, but that only blockage of ERα suppresses MMP-9 and MMP-13 levels induced by 17β-estradiol (E2). Overexpression of ERα but not ERβ enhances E2-induced MMP-9. Using the same loss-of-function and gain-of-function approaches, we demonstrate that E2 stimulates ERK activation through ERα and that inhibition of ERK phosphorylation reduces E2-induced MMP-9. Furthermore, we reveal that E2 promotes NF-κB and ELK-1 activation through ERα/ERK signaling and that knockdown of either one decreases the respective activity of these signaling mediators and MMP-9 expression induced by E2, indicating that both contribute to E2/ERα/ERK-mediated MMP-9 upregulation. This is supported by findings in which mutated binding sites of either NF-κB or ELK-1 in the MMP-9 promoter lead to a significant reduction of E2-stimulated promoter activity. Our findings provide novel molecular mechanisms for the understanding of E2-mediated upregulation of MMPs, having implications to pathophysiologic TMJ cartilage matrix turnover that may yield therapeutic intervention targets for TMJ disorders.

Indexed as

AnimalsCells, CulturedChondrocytesEstrogen Receptor alphaExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFemaleMatrix Metalloproteinase 13Matrix Metalloproteinase 9MiceMice, Inbred C57BLNF-kappa BPhosphorylationSignal TransductionTemporomandibular Joint DisordersTranscriptional ActivationEstrogen Receptor alphaExtracellular Signal-Regulated MAP KinasesMatrix Metalloproteinase 13Matrix Metalloproteinase 9MMP13 protein, humanNF-kappa Bestrogen receptor betaextracellular matrixextracellular signal-regulated kinase (ERK)nuclear factor kappa Bsignal transductiontemporomandibular joint disorder

Identifiers

PMID29621430
PMCPMC6055253
OpenAlexW2795768951

What OpenQuestion holds

Textmetadata
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.