Evidence map›Paper›PMID 42230587›Full record

ArticleNature communications2026

Large-scale molecular endotype discovery in synovial fluid reveals osteoarthritis as a single biological continuum.

T A Perry, Y Deng, P A Hulley, R A Maciewicz, J Mitchelmore, S Larsson, J Gogain, S Brachat, A Struglics, C T Appleton and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

24 authors.

T A Perry *Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK. thomas.perry@kennedy.ox.ac.uk.ORCID 0000-0002-0499-3033
Y Deng *Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.
P A HulleyNuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.ORCID 0000-0002-4994-2264
R A MaciewiczCentre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.ORCID 0000-0002-5371-7828
J MitchelmoreNovartis Biomedical Research, Basel, Switzerland.
S LarssonFaculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.ORCID 0000-0001-8626-9892
J GogainStandard BioTools (previously known as SomaLogic), Boulder, Colorado, USA.ORCID 0000-0001-7748-4822
S BrachatNovartis Biomedical Research, Basel, Switzerland.
A StruglicsFaculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.ORCID 0000-0003-4289-1393
C T AppletonDepartment of Medicine, University of Western Ontario, London, Ontario, Canada.ORCID 0000-0001-7148-0767
S KluzekNuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.ORCID 0000-0002-0696-7541
N K ArdenNuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK.ORCID 0000-0002-3452-3382
D FelsonSection of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA.ORCID 0000-0002-2668-2447
L BondiMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0002-7034-9406
M KapoorSchroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0001-7994-110X
L S LohmanderFaculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.ORCID 0000-0002-5424-9448
T J WeltingLaboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Maastricht, Netherlands.ORCID 0000-0001-8081-4466
D A WalshPain Centre Versus Arthritis, Advanced Pain Discovery Platform, and the NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0002-6316-5692
A M ValdesPain Centre Versus Arthritis, Advanced Pain Discovery Platform, and the NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0003-1141-4471
Luke Jostins-DeanCentre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.ORCID 0000-0002-2475-3969
Fiona E WattCentre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.ORCID 0000-0002-6066-7590
B D M TomMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0002-3335-9322
T L VincentCentre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK. tonia.vincent@kennedy.ox.ac.uk.ORCID 0000-0001-9594-7085
STEpUP OA Consortium

Funding

Medical Research Council MC UU 00002/2Wellcome Trust 208750/Z/17/Z
6 · The paper itself

Abstract

Knee osteoarthritis affects 40% of people during their lifetime, significantly impacting societies worldwide. Its molecular pathogenesis remains poorly understood and variable clinical phenotypes suggest it may be more than one disease. We established Synovial fluid To detect Endotypes by Unbiased Proteomics in OA (STEpUP OA) to search for molecular endotypes in knee OA synovial fluid, and to reveal key pathobiological pathways across 1361 individuals with knee OA. Using unsupervised clustering, a single cluster representing a biological continuum is observed, primarily driven by "Epithelial Mesenchymal Transition". Distinct molecular endotypes are not detected. "Angiogenesis", "Complement" and "Coagulation" are enriched for after stratification by clinical phenotype (obesity status, biological sex). Complement and coagulation are associated with the inflammatory marker, C-reactive protein. Associations with patient-reported knee pain are weaker. These findings support knee OA as a biological continuum, identify common and phenotype-enriched targetable pathways, and a rationale for stratification in clinical trial design.

Indexed as

Osteoarthritis, KneeSynovial FluidAgedBiomarkersC-Reactive ProteinEpithelial-Mesenchymal TransitionFemaleHumansMiddle AgedPhenotypeProteomicsBiomarkersC-Reactive Protein

Identifiers

PMID42230587
PMCPMC13230806

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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.