PXD035246

PXD035246 is an original dataset announced via ProteomeXchange.

Title	Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model
Description	Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/ grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. Statement of significance: Cartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILACbased proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:22.393.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Faull
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-11 13:30:47	ID requested
1	2022-07-18 08:31:38	announced
⏵ 2	2023-11-14 08:56:23	announced	2023-11-14: Updated project metadata.

Merrild NG, Holzmann V, Ariosa-Morejon Y, Faull PA, Coleman J, Barrell WB, Young G, Fischer R, Kelly DJ, Addison O, Vincent TL, Grigoriadis AE, Gentleman E, Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model. Acta Biomater, 149():179-188(2022) [pubmed]

submitter keyword: proteoglycan depletion,Cartilage repair, catabolic enzyme, tissue engineering

Eileen Gentleman
contact affiliation	Centre for Craniofacial and Regenerative Biology, King's College London, Guy's Hospital, United Kingdom
contact email	eileen.gentleman@kcl.ac.uk
lab head
Peter Faull
contact affiliation	The University of Texas at Austin
contact email	peter.faull@austin.utexas.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035246
     1. Label: PRIDE project
     2. Name: Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model