Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Perry, T A ; Deng, Y LU ; Hulley, P A ; Maciewicz, R A ; Mitchelmore, J ; Larsson, S LU ; Gogain, J ; Brachat, S ; Struglics, A LU and Appleton, C T , et al. (2026) In Nature Communications 17(1).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Synovial Fluid/metabolism, Osteoarthritis, Knee/metabolism, Proteomics/methods, Female, Biomarkers/metabolism, Phenotype, Middle Aged, Aged, Epithelial-Mesenchymal Transition, C-Reactive Protein/metabolism
in
Nature Communications
volume
17
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:105041163338
  • pmid:42230587
ISSN
2041-1723
DOI
10.1038/s41467-026-71632-4
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
c5bc1192-0281-4c14-a2d8-5f510b7406c5
date added to LUP
2026-07-23 16:34:37
date last changed
2026-09-04 07:15:31
@article{c5bc1192-0281-4c14-a2d8-5f510b7406c5,
  abstract     = {{<p>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.</p>}},
  author       = {{Perry, T A and Deng, Y and Hulley, P A and Maciewicz, R A and Mitchelmore, J and Larsson, S and Gogain, J and Brachat, S and Struglics, A and Appleton, C T and Kluzek, S and Arden, N K and Felson, D and Bondi, L and Kapoor, M and Lohmander, L S and Welting, T J and Walsh, D A and Valdes, A M and Jostins-Dean, Luke and Watt, Fiona E and Tom, B D M and Vincent, T L}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Synovial Fluid/metabolism; Osteoarthritis, Knee/metabolism; Proteomics/methods; Female; Biomarkers/metabolism; Phenotype; Middle Aged; Aged; Epithelial-Mesenchymal Transition; C-Reactive Protein/metabolism}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Large-scale molecular endotype discovery in synovial fluid reveals osteoarthritis as a single biological continuum}},
  url          = {{http://dx.doi.org/10.1038/s41467-026-71632-4}},
  doi          = {{10.1038/s41467-026-71632-4}},
  volume       = {{17}},
  year         = {{2026}},
}