PXD006999

PXD006999 is an original dataset announced via ProteomeXchange.

Title	Viperin; regulating chondrogenic differentiation via CXCL10 protein secretion
Description	Mutations in the RMRP gene are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in the RMRP gene lead to skeletal dysplasia. Viperin is a known substrate of RMRP. Since chondrogenic differentiation of the growth plate is required for development of the long bones, we hypothesized that viperin functions as a chondrogenic regulator downstream of RMRP. Viperin protein is expressed throughout the stages of chondrogenic differentiation in vivo. Viperin gene expression is increased during knockdown of Rmrp RNA in the ATDC5 model for chondrogenic differentiation. Viperin is expressed during ATDC5 chondrogenic differentiation. Viperin knockdown reduces, while viperin overexpression increases overall protein secretion, with CXCL10 identified as a potential target via mass spectrometry-proteomics. CXCL10 protein expression is reduced during knockdown and increased during overexpression of viperin and CXCL10 protein expression coincides with viperin expression in ATDC5 chondrogenic differentiation. Viperin knockdown induces, while viperin overexpression reduces TGFβ activity. Furthermore, viperin knockdown conditioned media increases, while viperin overexpression conditioned media reduces chondrogenic differentiation of ATDC5 cells. TGFβ target genes Pai1 and Smad7 are increased during knockdown and reduced during overexpression of viperin. Moreover, TGFβ activity is reduced when differentiating ATDC5 cells are exposed to CXCL10 and, acting as a viperin overexpression mimic, CXCL10 similarly reduces chondrogenic differentiation of ATDC5. Lastly, we show that in CHH patient cells, RMRP expression is reduced and viperin expression is increased, coinciding with reduced chondrogenic differentiation and increased CXCL10 expression, possibly explaining the CHH phenotype. Together our data show that viperin may play a pivotal role in chondrogenic differentiation, with potential consequences for cartilage-hair hypoplasia pathobiology.
HostingRepository	PRIDE
AnnounceDate	2019-02-15
AnnouncementXML	Submission_2019-02-18_01:12:39.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006999
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mandy Peffers
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-12 07:31:03	ID requested
1	2019-02-15 10:27:21	announced
⏵ 2	2019-02-18 01:12:40	announced	Updated publication reference for PubMed record(s): 30718282.

Steinbusch MMF, Caron MMJ, Surtel DAM, van den Akker GGH, van Dijk PJ, Friedrich F, Zabel B, van Rhijn LW, Peffers MJ, Welting TJM, The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion. J Biol Chem, 294(13):5121-5136(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: mouse, chondrogenic differentiation, viperin

Mandy J Peffers
contact affiliation	University of Liverpool
contact email	peffs@liv.ac.uk
lab head
Mandy Peffers
contact affiliation	University of Liverpool
contact email	peffs@liv.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006999
     1. Label: PRIDE project
     2. Name: Viperin; regulating chondrogenic differentiation via CXCL10 protein secretion