Evidence map›Paper›PMID 35459919›Full record

ArticleScientific reports2022

HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression.

Matt J Barter, Andrew Butcher, Hui Wang, Dimitra Tsompani, Martin Galler, Ellen L Rumsby, Kirsty L Culley, Ian M Clark, David A Young

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

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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

9 authors at 5 institutions in 1 country.

Matt J BarterBiosciences Institute, Central Parkway, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK. m.j.barter@ncl.ac.uk.
Andrew ButcherDepartment of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Hui WangArthritis and Regenerative Medicine Laboratory, Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK.
Dimitra TsompaniGSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Martin GallerBiosciences Institute, Central Parkway, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Ellen L RumsbyNorthern Care Alliance NHS Foundation Trust, Mayo Building, Salford Royal, Stott Lane, Salford, M6 8HD, UK.
Kirsty L CulleyAnglia Innovation Partnership LLP, Centrum, Norwich Research Park, Norwich, UK.
Ian M ClarkSchool of Biological Sciences, University of East Anglia, Norwich, UK.
David A YoungBiosciences Institute, Central Parkway, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Newcastle University · GBNorwich Research Park · GBUniversity of Aberdeen · GBUniversity of East Anglia · GBUniversity of Liverpool · GB

Funding

Arthritis Research UK 19424Medical Research Council JXR 10641, MR/P020941/1Medical Research Council MR/P020941/1Versus Arthritis 19424Versus Arthritis JXR 10641, MR/P020941/1
6 · The paper itself

Abstract

Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.

Indexed as

ArthritisChondrocytesAnimalsCells, CulturedGene ExpressionInterleukin-1betaMatrix Metalloproteinase 13Matrix MetalloproteinasesNF-kappa BInterleukin-1betaMatrix Metalloproteinase 13Matrix MetalloproteinasesNF-kappa B

Identifiers

PMID35459919
PMCPMC9033835
OpenAlexW4224285822

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.