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

Author:

Rydén Martin1ORCID,Turkiewicz Aleksandra1,Önnerfjord Patrik2,Tjörnstrand Jon13,Englund Martin1,Ali Neserin1

Affiliation:

1. Faculty of Medicine, Department of Clinical Sciences, Lund, Orthopedics Clinical Epidemiology Unit Lund University Lund Sweden

2. Faculty of Medicine, Department of Clinical Sciences, Lund Rheumatology and Molecular Skeletal Biology Lund University Lund Sweden

3. Department of Orthopedics Skåne University Hospital Lund Sweden

Abstract

AbstractSynovial 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.

Funder

H2020 European Research Council

Reumatikerförbundet

Foundation for Research in Rheumatology

Vetenskapsrådet

Greta och Johan Kocks stiftelser

Publisher

Wiley

Subject

Molecular Biology,Biochemistry

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