PXD048053

PXD048053 is an original dataset announced via ProteomeXchange.

Title	Proteolytic information flows from human knee osteoarthritic cartilage to synovial fluid and defines the roles of key drug targets -1
Description	Objectives: Proteolytic cartilage loss is a major mechanism of osteoarthritis (OA) pathogenesis but few joint breakdown biomarkers are currently available. We sought to determine the overlap of proteolytic peptides in OA cartilage and synovial fluid on a proteome-wide scale with the goals of increasing the biomarker repertoire and for attribution to individual proteases. Design: Proteins isolated from matched human OA cartilage and synovial fluid from 5 knees were analyzed by N-terminomics using Terminal Amine Isotopic Labeling of Substrates (TAILS), comprising labeling and enrichment of protein N-termini, high-resolution mass spectrometry and bioinformatics. Cartilage was digested with ADAMTS5, MMP13 and CMA1, and TAILS was used to identify their specific activities. Results: Analysis of matched knee OA cartilage and synovial fluid degradomes consistently demonstrated cartilage breakdown products in synovial fluid. Of over 20,000 cleaved peptides in the OA cartilage and synovial fluid degradomes, 677, originating from 153 proteins, were present in all samples, the majority arising from cartilage. ADAMTS5, MMP13 and CMA1 digestion of cartilage identified numerous cleavage sites for each protease, distinct cleavage site preferences, and peptides arising from the activities of these proteases in synovial fluid. Conclusions: Cartilage ECM-derived proteolytic fragments are consistently present in synovial fluid, many attributable to ADAMTS5, MMP13 and CMA1 activity, which showed little overlap with each other or the previously determined HtrA1activity profile. The present work increases the proteolytic biomarker space for OA investigation, showing that diverse proteases contribute to cartilage destruction, and that their individual contributions can be determined using multiple protease-specific biomarkers.
HostingRepository	PRIDE
AnnounceDate	2025-02-05
AnnouncementXML	Submission_2025-02-04_22:06:09.737.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sumit Bhutada
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	(R)-5-oxo-1; carbamoylated residue; acetylated residue; monohydroxylated residue
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-21 10:37:46	ID requested
⏵ 1	2025-02-04 22:06:10	announced

Bhutada S, Hoyle A, Piuzzi NS, Apte SS, Degradomics defines proteolysis information flow from human knee osteoarthritis cartilage to matched synovial fluid and the contributions of secreted proteases ADAMTS5, MMP13 and CMA1 to articular cartilage breakdown. Osteoarthritis Cartilage, 33(1):116-127(2025) [pubmed]

10.1016/j.joca.2024.09.002;

submitter keyword: Proteolysis, Synovial fluid, Cartilage, Protease, Proteomics,Osteoarthritis

Suneel Apte
contact affiliation	Lerner Research Institute, Cleveland Clinic
contact email	aptes@ccf.org
lab head
Sumit Bhutada
contact affiliation	Cleveland Clinic
contact email	bhutads@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048053
     1. Label: PRIDE project
     2. Name: Proteolytic information flows from human knee osteoarthritic cartilage to synovial fluid and defines the roles of key drug targets -1