Evidence map›Paper›PMID 26606969›Full record

ArticleScience translational medicine2015

Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis.

Sarah E Headland, Hefin R Jones, Lucy V Norling, Andrew Kim, Patricia R Souza, Elisa Corsiero, Cristiane D Gil, Alessandra Nerviani, Francesco Dell'Accio, Costantino Pitzalis and 3 more

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

Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 3 pooled it
10.7field-weighted citation impact, top 1% 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

204 citing papers in PubMed, 3 syntheses or guidelines pooled it, 316 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Review
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  6. Article
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  10. [Neutrophil-derived Microvesicles Regulate DNA Methylation of theSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
    Article
  11. Article
  12. Review
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  14. Article
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  17. Beyond Killing: The Overlooked Contribution of Neutrophils to Tissue Repair.International journal of molecular sciences · 2025
    Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Sarah E HeadlandWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Hefin R JonesWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Lucy V NorlingWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Andrew KimDepartment of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Patricia R SouzaWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Elisa CorsieroWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Cristiane D GilDepartment of Biology, Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University (UNESP), São José do Rio Preto 15054-000, Brazil.
Alessandra NervianiWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Francesco Dell'AccioWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Department of Rheumatology, Barts Health Trust, Bancroft Road, London E1 4DG, UK.
Costantino PitzalisWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Department of Rheumatology, Barts Health Trust, Bancroft Road, London E1 4DG, UK.
Sonia M OlianiDepartment of Biology, Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University (UNESP), São José do Rio Preto 15054-000, Brazil.
Lily Y JanDepartment of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Mauro PerrettiWilliam Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. m.perretti@qmul.ac.uk.
Howard Hughes Medical Institute · US

Funding

Molecular, Genetic & Physiological Studies of Calcium-activated Chloride ChannelsR01NS069229 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAN, LILY Y · 2011 to 2020
$3.5M
Arthritis Research UK 19654Arthritis Research UK 19909Cancer Research UK 20842Medical Research Council MR/K013068/1Medical Research Council MR/K013076/1NINDS NIH HHS R01 NS069229Wellcome TrustWellcome Trust 086867/Z/08Wellcome Trust 101604/Z/13/Z
6 · The paper itself

Abstract

Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophil-derived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis. To determine the function of MVs in inflammatory arthritis, toward the possibility of MV-based therapeutics, we examined the role of immune cell-derived MVs in rodent models and in human primary chondrocytes. In vitro, exogenous neutrophil-derived AnxA1(+) MVs activated anabolic gene expression in chondrocytes, leading to extracellular matrix accumulation and cartilage protection through the reduction in stress-adaptive homeostatic mediators interleukin-8 and prostaglandin E2. In vivo, intra-articular injection of AnxA1(+) MV lessened cartilage degradation caused by inflammatory arthritis. Arthritic mice receiving adoptive transfer of whole neutrophils displayed abundant MVs within cartilage matrix and revealed that MVs, but not neutrophils themselves, can penetrate cartilage. Mechanistic studies support a model whereby MV-associated AnxA1 interacts with its receptor FPR2 (formyl peptide receptor 2)/ALX, increasing transforming growth factor-β production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs, either directly or loaded with therapeutics, can be harnessed as a unique therapeutic strategy for protection in diseases associated with cartilage degeneration.

Indexed as

AnimalsArthritis, RheumatoidCartilage, ArticularHumansMiceNeutrophilsSynovial FluidTransforming Growth Factor betaTransforming Growth Factor beta

Identifiers

PMID26606969
PMCPMC6034622
OpenAlexW2271680371

What OpenQuestion holds

Textmetadata
LicenceTDM
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.