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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

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

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

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.

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

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

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TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis

Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis

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

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

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

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The study of inflammatory responses in mammalian macrophages with LPS stimulation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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