PXD028374

PXD028374 is an original dataset announced via ProteomeXchange.

Title	Ets-2 propagates IL-6 trans-signaling mediated osteoclast-like changes in human rheumatoid arthritis synovial fibroblast
Description	Interleukin-6 (IL-6) plays an important role in progressive bone loss in rheumatoid arthritis (RA). However, the molecular mechanisms through which IL-6 propels RA synovial fibroblasts (RASFs) to contribute to bone loss are not fully understood. In the present study, we investigated the effects of IL-6 and IL-6 receptor (IL-6/IL-6R induced trans-signaling in human RASFs. Treatment of human RASFs with IL-6 and IL-6 receptor (IL-6/IL-6R, 100 ng/ml each) alone or in combination with M-CSF (2 ng/ml) and RANKL (10 ng/ml) for 12 days resulted in the phenotypic changes to osteoclast-like features as determined by increase in TRAP staining and enhanced pit formation by ~3-fold in bone resorption assay in vitro. IL-6/IL-6R induced a dose-dependent increase in the expression of transcription factor Ets2 and enhanced its nuclear translocation in human RASFs. Interestingly, the untargeted proteomics analysis of the conditioned media from IL6/IL6R activated RASFs using Mass-Spectrometry (MS) technique and Trans-Proteomic Pipeline tool showed the production of 113 analytes unique to IL-6/IL-6R stimulation. Further analysis of the proteomics data using STRING database for pathway analysis showed the impact of IL-6/IL-6R on immunometabolic reprogramming of human RASFs towards osteoclast-like phenotype, which was partly mediated through Ets2. These preliminary studies identified a novel role of IL-6/IL-6R-mediated trans signaling in the metabolic reprogramming in RASFs that could potentially be targeted by inhibiting Ets2 to limit their role in bone resorption in RA.
HostingRepository	PRIDE
AnnounceDate	2022-02-21
AnnouncementXML	Submission_2022-02-21_07:10:38.308.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anil Singh
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:30:15	ID requested
⏵ 1	2022-02-21 07:10:38	announced

Dataset with its publication pending

submitter keyword: rheumatoid arthritis, synovial fibroblast, interleukin 6, osteoclast

Anil Kumar Singh
contact affiliation	Washington State University
contact email	anil.singh@wsu.edu
lab head
Anil Singh
contact affiliation	Washington State University
contact email	anil.singh@wsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028374
     1. Label: PRIDE project
     2. Name: Ets-2 propagates IL-6 trans-signaling mediated osteoclast-like changes in human rheumatoid arthritis synovial fibroblast