PXD039364-1
PXD039364 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Mocetinostat activates Kruppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis |
| Description | Kruppel-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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-07-20 |
| AnnouncementXML | Submission_2023-07-21_10:15:45.576.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Daniel McClatchy |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | unknown modification |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-01-11 16:20:48 | ID requested | |
| ⏵ 1 | 2023-07-21 10:15:45 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: KLF4, osteoarthritis |
Contact List
| Martin K Lotz, MD | |
|---|---|
| contact affiliation | Scripps Research |
| contact email | mlotz@scripps.edu |
| lab head | |
| Daniel McClatchy | |
| contact affiliation | TSRI |
| contact email | dmcclat@scripps.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000091049/ |
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