biostudies-literatureXu CNIAMS NIH HHS2141-2149https://www.ebi.ac.uk/biostudies/studies/S-EPMC6783374biostudies-literatureUnknown203(8)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 <i>FOXO3</i> locus. Several databases document <i>FOXO3</i> isoform2, an N-terminal truncated mutation of the full-length <i>FOXO3</i> However, the biological function of FOXO3 isoform2 is unclear. In this study, we established a conditional allele of <i>Foxo3</i> in mice that deletes the full-length <i>Foxo3</i> except isoform2, a close ortholog of the human <i>FOXO3</i> isoform2. Expression of Foxo3 isoform2 specifically in macrophage/osteoclast lineage suppresses osteoclastogenesis and leads to the osteopetrotic Journal of immunology (Baltimore, Md. : 1950)Identification of a Novel Role for Foxo3 Isoform2 in Osteoclastic Inhibition.PMC6783374R01 AR068970R01 AR071463R00 AR062047K99 AR062047Zhao BNg CXu CInoue KVitone GJfalseIdentification of a Novel Role for Foxo3 Isoform2 in Osteoclastic Inhibition.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 <i>FOXO3</i> locus. Several databases document <i>FOXO3</i> isoform2, an N-terminal truncated mutation of the full-length <i>FOXO3</i> However, the biological function of FOXO3 isoform2 is unclear. In this study, we established a conditional allele of <i>Foxo3</i> in mice that deletes the full-length <i>Foxo3</i> except isoform2, a close ortholog of the human <i>FOXO3</i> isoform2. Expression of Foxo3 isoform2 specifically in macrophage/osteoclast lineage suppresses osteoclastogenesis and leads to the osteopetrotic 2019-01-01T00:00:00Z2019 Oct2026-04-30T06:26:58.738Z2020-10-29T17:07:53ZS-EPMC67833743154102310.4049/jimmunol.1900707