Evidence map›Paper›PMID 26219353›Full record

ArticleBMC research notes2015

Matrix-metalloproteinase-9 is cleaved and activated by cathepsin K.

Jon Christensen, V Prasad Shastri

Open access · goldAbstract read
In one paragraph

Article in BMC research notes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

82 citing papers in PubMed, 136 citations in OpenAlex.

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22 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Jon ChristensenInstitute for Macromolecular Chemistry, University of Freiburg, Hermann-Staudinger-Haus Stefan-Meier-Straße 31, 79104, Freiburg, Germany. jonchris@mail.com.
V Prasad ShastriInstitute for Macromolecular Chemistry, University of Freiburg, Hermann-Staudinger-Haus Stefan-Meier-Straße 31, 79104, Freiburg, Germany. prasad.shastri@gmail.com.
University of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMatrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important.

resultsAcidification of osteoclast-conditioned media to pH 5 resulted in a fragment with a size corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to the molecular weight of active MMP-9, and showed MMP-9 activity. This activation was abrogated in the presence of CTSK inhibitor indicating that CTSK was responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231 cells also diminished MMP-9 activity compared to wild type control.

conclusionsHere we provide the first evidence that CTSK can cleave and activate MMP-9 in acidic environments such as seen in tumors and during bone resorption. This finding provides a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9 through extracellular physiological changes elucidated in this study reveals a protease-signaling network involving CTSK and MMP-9 and provides the impetus to explore ECM proteases as physiological markers and pharmacological targets.

Indexed as

Cathepsin KCell Line, TumorEnzyme ActivationEnzyme PrecursorsEpithelial CellsExtracellular SpaceGene ExpressionHumansHydrogen-Ion ConcentrationMatrix Metalloproteinase 9Protease InhibitorsRecombinant ProteinsRNA, Small InterferingSignal TransductionCathepsin KEnzyme PrecursorsMatrix Metalloproteinase 9pro-matrix metalloproteinase 9Protease InhibitorsRecombinant ProteinsRNA, Small Interfering

Identifiers

PMID26219353
PMCPMC4518881
OpenAlexW1547601942

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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.