Evidence map›Paper›PMID 29129649›Full record

ArticleOsteoarthritis and cartilage2018

TSG-6 - a double-edged sword for osteoarthritis (OA).

C-H Chou, D E Attarian, H-G Wisniewski, P A Band, V B Kraus

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
1.7field-weighted citation impact, top 16% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 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

5 authors at 3 institutions in 1 country.

C-H ChouDepartment of Pathology, Duke University, School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC 27701, USA.
D E AttarianDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
H-G WisniewskiMatrix Biology Institute, Fort Lee, NJ 07024, USA.
P A BandDepartment of Orthopedic Surgery, Biochemistry & Molecular Pharmacology, New York University, School of Medicine, and NYU Hospital for Joint Diseases, New York, NY 10003, USA.
V B KrausDuke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC 27701, USA. Electronic address: vbk@duke.edu.
Duke University · USMatrix Biology Institute · USNew York University Langone Orthopedic Hospital · US

Funding

Resource Core 3 - Metabolomics CoreP30AG028716 · NIA · DUKE UNIVERSITY · PI Virginia B Kraus · 2006 to 2026
$24.6M
NIA NIH HHS P30 AG028716
6 · The paper itself

Abstract

purposeTo explore mechanisms underlying the association of TSG-6 with osteoarthritis (OA) progression.

methodsTSG-6-mediated heavy chain (HC) transfer (TSG-6 activity) and its association with inflammatory mediators were quantified in knee OA (n=25) synovial fluids (SFs). Paired intact and damaged cartilages from the same individuals (20 tibial and 12 meniscal) were analyzed by qRT-PCR and immunohistochemistry (IHC) for gene and protein expression of TSG-6 and components of Inter-alpha-Inhibitor (IαI) and TSG-6 activity ± spiked in IαI. Primary chondrocyte cultures (n=5) ± IL1β or TNFα were evaluated for gene expression. The effects of TSG-6 activity on cartilage extracellular matrix (ECM) assembly were explored using quantitative hyaluronan (HA)-aggrecan binding assays.

resultsTSG-6 activity was significantly associated (R > 0.683, P < 0.0002) with inflammatory mediators including TIMP-1, A2M, MMP3, VEGF, VCAM-1, ICAM-1 and IL-6. Although TSG-6 protein and mRNA were highly expressed in damaged articular and meniscal cartilage and cytokine-treated chondrocytes, there was little or no cartilage expression of components of the IαI complex (containing HC1). By IHC, TSG-6 was present throughout lesioned cartilage but HC1 only at lesioned surfaces. TSG-6 impaired HA-aggrecan assembly, but TSG-6 mediated HA-HC formation reduced this negative effect.

conclusionsTSG-6 activity is a global inflammatory biomarker in knee OA SF. IαI, supplied from outside cartilage, only penetrates the cartilage surface, restricting TSG-6 activity (HC transfer) to this region. Therefore, unopposed TSG-6 in intermediate and deep regions of OA cartilage could possibly block matrix assembly, leading to futile synthesis and account for increased risk of OA progression.

Indexed as

AgedBiomarkersCartilage, ArticularCell Adhesion MoleculesCells, CulturedChondrocytesFemaleGene Expression RegulationHumansInflammation MediatorsMaleMiddle AgedOsteoarthritis, KneeRNA, MessengerSynovial FluidBiomarkersCell Adhesion MoleculesInflammation MediatorsRNA, MessengerTNFAIP6 protein, humanBiomarkerCartilage matrixHyaluronanInflammationOsteoarthritis progressionTSG-6

Identifiers

PMID29129649
PMCPMC5807166
OpenAlexW2605736759

What OpenQuestion holds

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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.