Dataset Information

Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network

ABSTRACT: Endochondral ossification is a physiological process related to the development of long bones, not only on the embryo phase, but also during postnatal development. Mouse cell lineage tracking studies and histology techniques focused on the metaphysis and growth plate area of long bones have described a phenotype transition from chondrocytes to bone cells. However, the molecular events involved in this phenotype transition is still undescribed. Aiming to reproduce this phenotype transition in in vitro cell culture context, primary mesenchymal progenitor cells have been isolated from femur heads, characterized, and cultured following a serial differentiation protocol, first using chondrogenic media and then osteogenic media. RNA samples were obtained at different cell culture time points and processed for RNAseq studies. Time points are: D7 corresponding to 7 days culture in chondrogenic media, D8 corresponding to samples obtained one day after switching to osteogenic media, D10 corresponding to samples obtained three days after switching to osteogenic media, and, D28 corresponding to samples obtained osteogenic terminal end point, compiling 7 days in chondrogenic media and 21 days in osteogenic media.

ORGANISM(S): Mus musculus

PROVIDER: GSE243090 | GEO | 2025/12/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project 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.

Dataset Information

Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets