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Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition

ABSTRACT: Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition

PROVIDER: PRJNA559068 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9915513.fastq.gz	Fastqsanger.gz
	SRR9915514.fastq.gz	Fastqsanger.gz

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Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition

Project description:We performed RNA-seq experiments, one with the WT control and Foxo3KO osteoclast precursors after RANKL stimulation to identify genes regulated by Foxo3 in osteoclast precursors.

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Identification of a Novel Role for Foxo3 Isoform2 in Osteoclastic Inhibition.

Project description:Foxo3 acts as an important central regulator that integrates signaling pathways and coordinates cellular responses to environmental changes. Recent studies show the involvement of Foxo3 in osteoclastogenesis and rheumatoid arthritis, which prompted us to further investigate the FOXO3 locus. Several databases document FOXO3 isoform2, an N-terminal truncated mutation of the full-length FOXO3 However, the biological function of FOXO3 isoform2 is unclear. In this study, we established a conditional allele of Foxo3 in mice that deletes the full-length Foxo3 except isoform2, a close ortholog of the human FOXO3 isoform2. Expression of Foxo3 isoform2 specifically in macrophage/osteoclast lineage suppresses osteoclastogenesis and leads to the osteopetrotic phenotype in mice. Mechanistically, Foxo3 isoform2 enhances the expression of type I IFN response genes to RANKL stimulation and thus inhibits osteoclastogenesis via endogenous IFN-β-mediated feedback inhibition. Our findings identify, to our knowledge, the first known biological function of Foxo3 isoform2 that acts as a novel osteoclastic inhibitor in bone remodeling.

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Identification of a FOXO3/IRF7 circuit that limits inflammatory sequelae of antiviral responses (ChIP-Seq)

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