Evidence map›Paper›PMID 29720234›Full record

ArticleArthritis research & therapy2018

Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation.

Charlotte H Hulme, Emma L Wilson, Heidi R Fuller, Sally Roberts, James B Richardson, Pete Gallacher, Mandy J Peffers, Sally L Shirran, Catherine H Botting, Karina T Wright

Abstract read
In one paragraph

Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Cell therapy for cartilage repair.Emerging topics in life sciences · 2021
    Review
  5. Article
  6. Review
  7. 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.

Charlotte H HulmeInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
Emma L WilsonRobert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, SY10 7AG, UK.
Heidi R FullerInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
Sally RobertsInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
James B RichardsonInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
Pete GallacherInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
Mandy J PeffersInstitute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
Sally L ShirranBSRC Mass Spectrometry and Proteomics Facility, University of St Andrews, North Haugh, Fife, KY16 9ST, UK.
Catherine H BottingBSRC Mass Spectrometry and Proteomics Facility, University of St Andrews, North Haugh, Fife, KY16 9ST, UK.
Karina T WrightInstitute of Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK. Karina.Wright@rjah.nhs.uk.

Funding

Arthritis Research UK 19429Arthritis Research UK 20815Arthritis Research UK 21122Medical Research Council MR/P020941/1Versus Arthritis 18480Versus Arthritis 19429Wellcome TrustWellcome Trust 0944/Z/10/Z
6 · The paper itself

Abstract

backgroundAutologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood.

methodsIsobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses.

resultsiTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling.

conclusionsSeveral candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.

Indexed as

AdolescentAdultAgedAged, 80 and overChondrocytesFemaleHumansMaleMiddle AgedOutcome Assessment, Health CareProtein Interaction MapsProteomeProteomicsSynovial FluidTransplantation, AutologousYoung AdultProteomeAutologous chondrocyte implantation (ACI)Cartilage repairComplement C1S subcomponentiTRAQ proteomicsLabel-free quantitation proteomicsMatrix metalloproteinase 3MMP3Synovial fluid

Identifiers

PMID29720234
PMCPMC5932832

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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.