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Identification and quantification of degradome components in human synovial fluid reveals an increased proteolytic activity in knee osteoarthritis patients vs controls

Rydén, Martin LU orcid ; Turkiewicz, Aleksandra LU ; Önnerfjord, Patrik LU orcid ; Tjörnstrand, Jon LU ; Englund, Martin LU orcid and Ali, Neserin LU orcid (2023) In Proteomics 23(15).
Abstract

Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery and controls, that is, deceased donors without known knee disease were previously run using liquid chromatography mass spectrometry (LC-MS). This data was used to perform new database searches generating results for non-tryptic and semi-tryptic peptides for studies of degradomics in OA. We used linear mixed models to estimate differences in... (More)

Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery and controls, that is, deceased donors without known knee disease were previously run using liquid chromatography mass spectrometry (LC-MS). This data was used to perform new database searches generating results for non-tryptic and semi-tryptic peptides for studies of degradomics in OA. We used linear mixed models to estimate differences in peptide-level expression between the two groups. Known proteolytic events (from the MEROPS peptidase database) were mapped to the dataset, allowing the identification of potential proteases and which substrates they cleave. We also developed a peptide-centric R tool, proteasy, which facilitates analyses that involve retrieval and mapping of proteolytic events. We identified 429 differentially abundant peptides. We found that the increased abundance of cleaved APOA1 peptides is likely a consequence of enzymatic degradation by metalloproteinases and chymase. We identified metalloproteinase, chymase, and cathepsins as the main proteolytic actors. The analysis indicated increased activity of these proteases irrespective of their abundance.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proteomics
volume
23
issue
15
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:37226369
  • scopus:85160043920
ISSN
1615-9861
DOI
10.1002/pmic.202300040
language
English
LU publication?
yes
additional info
© 2023 The Authors. Proteomics published by Wiley-VCH GmbH.
id
b761be58-d282-4af6-8f37-3e09f44fbb0e
date added to LUP
2023-07-11 15:16:23
date last changed
2024-12-15 00:19:14
@article{b761be58-d282-4af6-8f37-3e09f44fbb0e,
  abstract     = {{<p>Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery and controls, that is, deceased donors without known knee disease were previously run using liquid chromatography mass spectrometry (LC-MS). This data was used to perform new database searches generating results for non-tryptic and semi-tryptic peptides for studies of degradomics in OA. We used linear mixed models to estimate differences in peptide-level expression between the two groups. Known proteolytic events (from the MEROPS peptidase database) were mapped to the dataset, allowing the identification of potential proteases and which substrates they cleave. We also developed a peptide-centric R tool, proteasy, which facilitates analyses that involve retrieval and mapping of proteolytic events. We identified 429 differentially abundant peptides. We found that the increased abundance of cleaved APOA1 peptides is likely a consequence of enzymatic degradation by metalloproteinases and chymase. We identified metalloproteinase, chymase, and cathepsins as the main proteolytic actors. The analysis indicated increased activity of these proteases irrespective of their abundance.</p>}},
  author       = {{Rydén, Martin and Turkiewicz, Aleksandra and Önnerfjord, Patrik and Tjörnstrand, Jon and Englund, Martin and Ali, Neserin}},
  issn         = {{1615-9861}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{15}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Proteomics}},
  title        = {{Identification and quantification of degradome components in human synovial fluid reveals an increased proteolytic activity in knee osteoarthritis patients vs controls}},
  url          = {{http://dx.doi.org/10.1002/pmic.202300040}},
  doi          = {{10.1002/pmic.202300040}},
  volume       = {{23}},
  year         = {{2023}},
}