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PXD039364-1

PXD039364 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMocetinostat activates Kruppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis
DescriptionKruppel-like factor-4 (KLF4) is a central transcription factor upregulating regenerative and protective functions in joint tissue cells. To explore novel therapeutic candidates for osteoarthritis (OA), high-throughput screening (HTS) with 11,948 compounds was per-formed using a reporter cell line detecting endogenous KLF4 activation. Eighteen com-pounds were identified through the HTS and confirmed in a secondary screen. Among them, mocetinostat, a class I histone deacetylase inhibitor, had the best biological activi-ties. Mocetinostat upregulated chondrogenic genes in human chondrocytes, meniscal cells, and mesenchymal stem cells, while it down-regulated hypertrophic, inflammatory and cat-abolic genes in those cells and synoviocytes. Intraperitoneal administration of mocetino-stat into mice reduced severity of OA-associated changes in cartilage, meniscus and syno-vium and improved pain behaviors. Global gene expression and proteomics analyses re-vealed that regenerative and protective effects of mocetinostat depended on peroxisome proliferator-activated receptor gamma coactivator 1-alpha. These findings qualify mocetino-stat as a potential candidate for disease modifying OA drugs.
HostingRepositoryMassIVE
AnnounceDate2023-07-20
AnnouncementXMLSubmission_2023-07-21_10:15:45.576.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDaniel McClatchy
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListunknown modification
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-11 16:20:48ID requested
12023-07-21 10:15:45announced
Publication List
no publication
Keyword List
submitter keyword: KLF4, osteoarthritis
Contact List
Martin K Lotz, MD
contact affiliationScripps Research
contact emailmlotz@scripps.edu
lab head
Daniel McClatchy
contact affiliationTSRI
contact emaildmcclat@scripps.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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