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RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk

ABSTRACT: RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk

PROVIDER: PRJNA559493 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9938350.fastq.gz	Fastqsanger.gz
	SRR9938360.fastq.gz	Fastqsanger.gz
	SRR9938370.fastq.gz	Fastqsanger.gz
	SRR9938380.fastq.gz	Fastqsanger.gz
	SRR9938390.fastq.gz	Fastqsanger.gz

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RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [ChIP-seq]

Project description:RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [ChIP-seq]

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RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [RNA-seq]

Project description:RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [RNA-seq]

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RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [RNA-seq]

Project description:In this study, we focused on elucidating the role of Ring Finger Protein 40 (RNF40) in bone development by using a conditional knockout mouse approach during different stages of osteoblast (OB) differentiation and maturation. RNF40 forms an obligate E3 ubiquitin ligase complex together with RNF20 and mediates the monoubiquitination of lysine 120 of histone H2B (H2BK120ub1). We provide evidence that RNF40 regulates OB differentiation in a stage-dependent manner. Additionally, we show that RNF40 is required for bone cell crosstalk whereby loss of RNF40 leads to a reduction in osteoclast numbers and function through modulation of vitamin D receptor (VDR)-induced Rankl expression in OBs. Taken together, these data imply an important role of RNF40-mediated H2Bub1 in bone formation and remodeling and provide a basis for further investigation of its anti-resorptive potential for the treatment of conditions such as osteoporosis or cancer-associated osteolysis. In this study we show that RNF40 is required in earlier stages of osteoblast differentiation and is involved in bone cell crosstalk by regulating vitamin D induced Rankl expression

2021-02-24 | GSE135628 | GEO

RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [ChIP-seq]

2021-02-24 | GSE135627 | GEO

RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk.

Project description:The role of histone ubiquitination in directing cell lineage specification is only poorly understood. Our previous work indicated a role of the histone 2B ubiquitin ligase RNF40 in controlling osteoblast differentiation in vitro. Here, we demonstrate that RNF40 has a stage-dependent function in controlling osteoblast differentiation in vivo. RNF40 expression is essential for early stages of lineage specification, but is dispensable in mature osteoblasts. Paradoxically, while osteoblast-specific RNF40 deletion led to impaired bone formation, it also resulted in increased bone mass due to impaired bone cell crosstalk. Loss of RNF40 resulted in decreased osteoclast number and function through modulation of RANKL expression in OBs. Mechanistically, we demonstrate that Tnfsf11 (encoding RANKL) is an important target gene of H2B monoubiquitination. These data reveal an important role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling and provide a basis for exploring this pathway for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.

| S-EPMC7862367 | biostudies-literature

RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-24 | GSE135629 | GEO

Itaconate mediates a metabolic crosstalk between osteoclasts and osteoblasts

Project description:Itaconate mediates a metabolic crosstalk between osteoclasts and osteoblasts

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Itaconate mediates an immunometabolic crosstalk between osteoclasts and osteoblasts

Project description:Itaconate mediates an immunometabolic crosstalk between osteoclasts and osteoblasts

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Itaconate mediates a metabolic crosstalk between osteoclasts and osteoblasts

Project description:Bone remodeling is a highly dynamic process dependent on the precise coordination of osteoblasts and hematopoietic-cell derived osteoclasts. Emerging evidence indicates that cellular differentiation is associated with a metabolic rewiring in conjunction with the acquisition of specific effector functions. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. We show that during differentiation preosteoclasts rearrange their tricarboxylic acid (TCA) cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterized by induction of immunoresponsive gene 1 (Irg1) and production of itaconate, which accumulates intra- and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generationin vitroandin vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation, reducing proliferation and shifting ATP production from mitochondrial respiration to glycolysis. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely,Irg1deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognized regulator of the crosstalk between osteoclasts and osteoblasts

2024-07-24 | GSE236452 | GEO

Regulation of gene expression by WAC/RNF20/RNF40 in HEK293A cells

Project description:WAC is a known positive regulator of (macro)autophagy. WAC also forms a complex with RNF20/RNF40 to promote H2B monoubiquitination and hence to affect transcriptional regulation. This study addresses whether the WAC/RNF20/RNF40 complex regulates autophagy through effects on gene expression.

2015-12-17 | GSE66475 | GEO

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