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Proteomic clustering reveals the kinetics of disease biomarkers in bovine and human models of post-traumatic osteoarthritis

Black, Rebecca Mae ; Wang, Yang ; Struglics, André LU ; Lorenzo, Pilar LU ; Chubinskaya, Susan ; Grodzinsky, Alan J. LU and Önnerfjord, Patrik LU orcid (2021) In Osteoarthritis and Cartilage Open 3(4).
Abstract

Objectives: In this study, we apply a clustering method to proteomic data sets from bovine and human models of post-traumatic osteoarthritis (PTOA) to distinguish clusters of proteins based on their kinetics of release from cartilage and examined these groups for PTOA biomarker candidates. We then quantified the effects of dexamethasone (Dex) on the kinetics of release of the cartilage media proteome. Design: Mass spectrometry was performed on sample medium collected from two separate experiments using juvenile bovine and human cartilage explants (3 samples/treatment condition) during 20- or 21-day treatment with inflammatory cytokines (TNF-α, IL-6, sIL-6R) with or without a single compressive mechanical injury. All samples were... (More)

Objectives: In this study, we apply a clustering method to proteomic data sets from bovine and human models of post-traumatic osteoarthritis (PTOA) to distinguish clusters of proteins based on their kinetics of release from cartilage and examined these groups for PTOA biomarker candidates. We then quantified the effects of dexamethasone (Dex) on the kinetics of release of the cartilage media proteome. Design: Mass spectrometry was performed on sample medium collected from two separate experiments using juvenile bovine and human cartilage explants (3 samples/treatment condition) during 20- or 21-day treatment with inflammatory cytokines (TNF-α, IL-6, sIL-6R) with or without a single compressive mechanical injury. All samples were incubated with or without 100 ​nM Dex. Clustering was performed on the correlation between normalized averaged release vectors for each protein. Results: Our proteomic method identified the presence of distinct clusters of proteins based on the kinetics of their release over three weeks of culture. Clusters of proteins with peak release after one to two weeks had biomarker candidates with increased release compared to control. Dex rescued some of the changes in protein release kinetics the level of control, and in all conditions except control, there was late release of immune-related proteins. Conclusions: We demonstrate a clustering method applied to proteomic data sets to identify and validate biomarkers of early PTOA progression and explore the relationships between the release of spatially related matrix components. Dex restored the kinetics of release to many matrix components, but not all factors that contribute to cartilage homeostasis.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cartilage matrix, Cytokines, Dexamethasone, Mass spectrometry, Post-traumatic osteoarthritis, Proteomics
in
Osteoarthritis and Cartilage Open
volume
3
issue
4
article number
100191
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85150478280
ISSN
2665-9131
DOI
10.1016/j.ocarto.2021.100191
language
English
LU publication?
yes
additional info
Funding Information: Supported by grants and NIH-NCATS UG3/UH3 TR002186 and NIH-NIBIB R01 EB026344 (AJG), A∗STAR (Singapore) Fellowship and Poitras Pre-doctoral Fellowship (YW), the Rush Klaus Kuettner Endowed Chair (SC), the Swedish Research Council (2014–3303), the Swedish Rheumatism Association (AS and PÖ), the Olle Engkvist Foundation (PÖ), the Krapperup Foundation (PÖ), the Alfred Österlund Foundation (AS, PÖ), the Greta & Johan Kock and Crafoord Foundations (AS, PÖ). The authors acknowledge Gift of Hope Organ & Tissue Donor Network (Itasca, IL) and donors' families. Publisher Copyright: © 2021 The Author(s)
id
dc1c2a3b-c5eb-45b6-8162-413c766d5d88
date added to LUP
2023-08-16 13:42:57
date last changed
2023-08-16 14:31:45
@article{dc1c2a3b-c5eb-45b6-8162-413c766d5d88,
  abstract     = {{<p>Objectives: In this study, we apply a clustering method to proteomic data sets from bovine and human models of post-traumatic osteoarthritis (PTOA) to distinguish clusters of proteins based on their kinetics of release from cartilage and examined these groups for PTOA biomarker candidates. We then quantified the effects of dexamethasone (Dex) on the kinetics of release of the cartilage media proteome. Design: Mass spectrometry was performed on sample medium collected from two separate experiments using juvenile bovine and human cartilage explants (3 samples/treatment condition) during 20- or 21-day treatment with inflammatory cytokines (TNF-α, IL-6, sIL-6R) with or without a single compressive mechanical injury. All samples were incubated with or without 100 ​nM Dex. Clustering was performed on the correlation between normalized averaged release vectors for each protein. Results: Our proteomic method identified the presence of distinct clusters of proteins based on the kinetics of their release over three weeks of culture. Clusters of proteins with peak release after one to two weeks had biomarker candidates with increased release compared to control. Dex rescued some of the changes in protein release kinetics the level of control, and in all conditions except control, there was late release of immune-related proteins. Conclusions: We demonstrate a clustering method applied to proteomic data sets to identify and validate biomarkers of early PTOA progression and explore the relationships between the release of spatially related matrix components. Dex restored the kinetics of release to many matrix components, but not all factors that contribute to cartilage homeostasis.</p>}},
  author       = {{Black, Rebecca Mae and Wang, Yang and Struglics, André and Lorenzo, Pilar and Chubinskaya, Susan and Grodzinsky, Alan J. and Önnerfjord, Patrik}},
  issn         = {{2665-9131}},
  keywords     = {{Cartilage matrix; Cytokines; Dexamethasone; Mass spectrometry; Post-traumatic osteoarthritis; Proteomics}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Elsevier}},
  series       = {{Osteoarthritis and Cartilage Open}},
  title        = {{Proteomic clustering reveals the kinetics of disease biomarkers in bovine and human models of post-traumatic osteoarthritis}},
  url          = {{http://dx.doi.org/10.1016/j.ocarto.2021.100191}},
  doi          = {{10.1016/j.ocarto.2021.100191}},
  volume       = {{3}},
  year         = {{2021}},
}