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Creb5 establishes the competence for Prg4 expression in articular cartilage

ABSTRACT: Creb5 establishes the competence for Prg4 expression in articular cartilage

PROVIDER: PRJNA547776 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9215180.fastq.gz	Fastqsanger.gz
	SRR9215181.fastq.gz	Fastqsanger.gz
	SRR9215182.fastq.gz	Fastqsanger.gz
	SRR9215183.fastq.gz	Fastqsanger.gz
	SRR9215184.fastq.gz	Fastqsanger.gz

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Creb5 establishes the competence for Prg4 expression in articular cartilage

Project description:Zhang et al. identify Creb5 as a transcription factor that is required for induction of Prg4 expression by TGFbeta and EGFR ligands. They show that Creb5 directly binds to two Prg4 promoter-proximal regulatory elements, working together with a more distal regulatory element to drive induction of Prg4 by TGFbeta. These findings provide new insight into the molecular regulation of Prg4 expression in superficial zone articular chondrocytes.

2021-03-16 | GSE132379 | GEO

Creb5 coordinates synovial joint formation with the genesis of articular cartilage

Project description:While prior work has established that articular cartilage arises from Prg4-expressing perichondrial cells, it is not clear how this process is specifically restricted to the perichondrium of synovial joints. We document that the transcription factor Creb5 is necessary to initiate the expression of signaling molecules that both direct the formation of synovial joints and guide perichondrial tissue to form articular cartilage instead of bone. Creb5 promotes the generation of articular chondrocytes from perichondrial precursors in part by inducing expression of Wif1, which blocks a Wnt5a autoregulatory loop in the perichondrium. Postnatal deletion of Creb5 in the articular cartilage leads to loss of both flat superficial zone articular chondrocytes coupled with a loss of both Prg4 and Wif1 expression; and a non-cell autonomous up-regulation of Ctgf. Our findings indicate that Creb5 promotes both joint formation and the subsequent development of articular chondrocytes by disrupting a Wnt5a positive-feedback loop in the perichondrium.

2022-11-07 | GSE181883 | GEO

Creb5 establishes the competence for Prg4 expression in articular cartilage.

Project description:A hallmark of cells comprising the superficial zone of articular cartilage is their expression of lubricin, encoded by the Prg4 gene, that lubricates the joint and protects against the development of arthritis. Here, we identify Creb5 as a transcription factor that is specifically expressed in superficial zone articular chondrocytes and is required for TGF-β and EGFR signaling to induce Prg4 expression. Notably, forced expression of Creb5 in chondrocytes derived from the deep zone of the articular cartilage confers the competence for TGF-β and EGFR signals to induce Prg4 expression. Chromatin-IP and ATAC-Seq analyses have revealed that Creb5 directly binds to two Prg4 promoter-proximal regulatory elements, that display an open chromatin conformation specifically in superficial zone articular chondrocytes; and which work in combination with a more distal regulatory element to drive induction of Prg4 by TGF-β. Our results indicate that Creb5 is a critical regulator of Prg4/lubricin expression in the articular cartilage.

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Creb5 coordinates synovial joint formation with the genesis of articular cartilage

Project description:Creb5 coordinates synovial joint formation with the genesis of articular cartilage

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Expression data from articular and growth plate cartilage

Project description:The aim of the current study was to identify molecular markers for articular cartilage that can be used for the quality control of tissue engineered cartilage. Therefore a genom-wide expression analysis was performed using RNA isolated from articular and growth plate cartilage, both extracted from the knee joints of minipigs. Keywords: Native material or primary cells isolated from articular cartilage and growth plate cartilage Articular and growth plate cartilage were taken for RNA extraction and hybridization on Affymetrix microarrays. Furthermore chondrocytes from each type of cartilage were isolated and cell culture was started and terminated at day 10 or day 20. Total RNA from cultivated cells was extracted, and hybridization on Affymetrix microarrays was performed.

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