Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171843 | GEO | 2022/03/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis.

Project description:It is well-established that receptor activator of NF-κB ligand (RANKL) is the inducer of physiological osteoclast differentiation. However, the specific drivers and mechanisms driving inflammatory osteoclast differentiation under pathological conditions remain obscure. This is especially true given that inflammatory cytokines such as tumor necrosis factor (TNF) demonstrate little to no ability to directly drive osteoclast differentiation. Here, we found that transforming growth factor β (TGFβ) priming enables TNF to effectively induce osteoclastogenesis, independently of the canonical RANKL pathway. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not basal, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms the macrophage response to TNF by remodeling chromatin accessibility and histone modifications, and enables TNF to induce a previously unrecognized non-canonical osteoclastogenic program, which includes suppression of the TNF-induced IRF1-IFNβ-IFN-stimulated-gene axis, IRF8 degradation and B-Myb induction. These mechanisms are active in rheumatoid arthritis, in which TGFβ level is elevated and correlates with osteoclast activity. Our findings identify a TGFβ/TNF-driven inflammatory osteoclastogenic program, and may lead to development of selective treatments for inflammatory osteolysis.

| S-EPMC9263175 | biostudies-literature

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [ATAC-seq]

Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.

2022-03-24 | GSE171841 | GEO

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [RNA-seq]

2022-03-24 | GSE171839 | GEO

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [CUT&RUN]

2022-03-24 | GSE171842 | GEO

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis

Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis

| PRJNA721177 | ENA

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [RNA-seq]

Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [RNA-seq]

| PRJNA721180 | ENA

TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [ATAC-seq]