Evidence map›Paper›PMID 27519904›Full record

ArticleArthritis research & therapy2016

Suppression of the inflammatory response by disease-inducible interleukin-10 gene therapy in a three-dimensional micromass model of the human synovial membrane.

Mathijs G A Broeren, Marieke de Vries, Miranda B Bennink, Onno J Arntz, Peter L E M van Lent, Peter M van der Kraan, Wim B van den Berg, Frank H J van den Hoogen, Marije I Koenders, Fons A J van de Loo

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs).Therapeutic advances in musculoskeletal disease · 2022
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Adipose tissue is a critical regulator of osteoarthritis.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Review
  11. Article
  12. CXCL10 is upregulated in synovium and cartilage following articular fracture.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018
    Article
  13. Protective Role of the MER Tyrosine KinaseFrontiers in immunology · 2018
    Article
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

10 authors at 3 institutions in 1 country.

Mathijs G A BroerenExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Marieke de VriesExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Miranda B BenninkExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Onno J ArntzExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Peter L E M van LentExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Peter M van der KraanExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Wim B van den BergExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Frank H J van den HoogenExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Marije I KoendersExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Fons A J van de LooExperimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. fons.vandeloo@radboudumc.nl.
Radboud Institute for Molecular Life Sciences · NLRadboud University Medical Center · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGene therapy has the potential to provide long-term production of therapeutic proteins in the joints of osteoarthritis (OA) patients. The objective of this study was to analyse the therapeutic potential of disease-inducible expression of anti-inflammatory interleukin-10 (IL-10) in the three-dimensional micromass model of the human synovial membrane.

methodsSynovial tissue samples from OA patients were digested and the cells were mixed with Matrigel to obtain 3D micromasses. The CXCL10 promoter combined with the firefly luciferase reporter in a lentiviral vector was used to determine the response of the CXCL10 promoter to tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and lipopolysaccharide (LPS). The effects of recombinant IL-10 on gene expression were determined by quantitative PCR. The production of IL-10 from the CXCL10p-IL10 vector and the effects on pro-inflammatory cytokine production were assessed by multiplex ELISA.

resultsMicromasses made from whole synovial membrane cell suspensions form a distinct surface composition containing macrophage and fibroblast-like synoviocytes thus mimicking the synovial lining. This lining can be transduced by lentiviruses and allow CXCL-10 promoter-regulated transgene expression. Adequate amounts of IL-10 transgene were produced after stimulation with pro-inflammatory factors able to reduce the production of synovial IL-1β and IL-6.

conclusionsSynovial micromasses are a suitable model to test disease-regulated gene therapy approaches and the CXCL10p-IL10 vector might be a good candidate to decrease the inflammatory response implicated in the pathogenesis of OA.

Indexed as

Chemokine CXCL10Enzyme-Linked Immunosorbent AssayFemaleFlow CytometryGenetic TherapyGenetic VectorsHumansInterleukin-10LentivirusMaleMicroscopy, ConfocalOsteoarthritisPromoter Regions, GeneticReal-Time Polymerase Chain ReactionSynovial MembraneTissue Culture TechniquesChemokine CXCL10CXCL10 protein, humanIL10 protein, humanInterleukin-10CytokinesGene therapyInflammationMicromassesOsteoarthritisSynovium

Identifiers

PMID27519904
PMCPMC4983024
OpenAlexW2508826894

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.