PXD027215

PXD027215 is an original dataset announced via ProteomeXchange.

Title	Metabolic reprogramming: Targeting inhibition of osteoarthritis-induced pyruvate dehydrogenase kinase expression preserves mitochondrial respiration
Description	Fibroblast-like synoviocytes (FLS) maintain the structural and dynamic integrity of joints. Additionally, FLS have been identified as key drivers of joint destruction in osteoarthritis (OA). Pathogenic THY1+ FLS are classified as invasively proliferative cells. However, little is known about the metabolic changes of FLS in the pathogenesis of OA. Here, we demonstrate functional, proteomic, and metabolic characteristics of inflammation-exposed FLS compared with unexposed fibroblast-like mesenchymal stromal cells (MSCs) from patients with OA. Analysis of FLS and MSC proteomes revealed 592 differentially expressed proteins. Although both cell types were indistinguishable according to classical markers, pathway analysis revealed that pyruvate dehydrogenase kinase (PDK) 3 is highly expressed only in proliferative FLS. Inhibition of PDKs by dichloroacetate significantly shifted glycolysis to oxidative phosphorylation while reducing proliferation without causing cell death. Therefore, reprogramming FLS metabolism from glycolysis to mitochondrial respiration by inhibiting PDK isoforms might be a new approach to treat transformed FLS in OA
HostingRepository	PRIDE
AnnounceDate	2022-03-31
AnnouncementXML	Submission_2022-03-31_12:10:26.011.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-09 08:24:20	ID requested
⏵ 1	2022-03-31 12:10:26	announced

Dataset with its publication pending

submitter keyword: synovial fibroblasts, osteoarthritis, pyruvate dehydrogenase kinase, metabolism

Philipp Mertins
contact affiliation	Berlin Institute of Health at Charité, Proteomics Platform, Berlin, Germany
contact email	philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027215
     1. Label: PRIDE project
     2. Name: Metabolic reprogramming: Targeting inhibition of osteoarthritis-induced pyruvate dehydrogenase kinase expression preserves mitochondrial respiration