Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE135479 | GEO | 2019/09/25
REPOSITORIES: GEO
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Project description:We performed RNA-seq experiments, one with the WT control and Mir182ΔM/ΔM osteoclast precursors at baseline and after RANKL stimulation, the other with miR-182 gain of function approach using the control and Mir182mTg BMMs, to identify genes regulated by miR-182 in osteoclast precursors.
2018-09-04 | GSE108721 | GEO
Project description:Identification of a novel role for FoxO3 isoform2 in osteoclastic inhibition
| PRJNA559068 | ENA
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.
| S-EPMC6783374 | biostudies-literature
Project description:Comparison of gene expression of the osteoclast precursor myeloid blast seeded on plastic and on bone, primed with M-CSF for 4 days and culture with M-CSF and RANKL for 1 day. Osteoclasts and macrophages share progenitors that must receive decisive lineage signals driving them into their respective differentiation routes. Macrophage colony stimulation factor M-CSF is a common factor; bone is likely the stimulus for osteoclast differentiation. To elucidate the effect of both, shared mouse bone marrow precursor myeloid blast was pre-cultured with M-CSF on plastic and on bone. M-CSF priming prior to stimulation with M-CSF and osteoclast differentiation factor RANKL resulted in a complete loss of osteoclastogenic potential without bone. This coincided with a steeply decreased expression of osteoclast genes TRACP and DC-STAMP, but an increased expression of the macrophage markers F4/80 and CD11b. Compellingly, M-CSF priming on bone accelerated the osteoclastogenic potential: M-CSF primed cells that had received only one day M-CSF and RANKL and were grown on bone already expressed an array of genes that are associated with osteoclast differentiation and these cells differentiated into osteoclasts within 2 days. This implies that adhesion to bone dictates the fate of osteoclast precursors. Common macrophage-osteoclast precursors may become insensitive to differentiate into osteoclasts and regain osteoclastogenesis when bound to bone or when in the vicinity of bone. Two conditions: Osteoclast precursors on plastic and on bone, n=4, dye swap
2014-06-02 | E-GEOD-58146 | biostudies-arrayexpress
Project description:We performed RNA-seq experiments, one with the WT control and Ga13ΔM/ΔM osteoclast precursors at baseline and after RANKL stimulation.
2019-03-20 | GSE116550 | GEO
Project description:We used microarrays to understand the effect miR-155 has on osteoclast differentiation. RAW264.7 cells were grown in a-MEM supplemented with 10% FBS and antibiotics. mRNA extracted from wild-type RAW264.7 cells and miR-155 mis-expressing cells either before or after 72 hr of stimulation with 20ng/ml RANKL and M-CSF to induce osteoclast differentiation.
2010-07-30 | E-GEOD-16749 | biostudies-arrayexpress
Project description:Expressions of mRNA in osteoclast precursors treated with RANKL and M-CSF for 0, 24, and 72 h. We used DNA microarray to analyze the changes in mRNA expressions during osteoclastogegesis. Experiment Overall Design: Osteoclast precursors were induced from mouse bone marrow cells by M-CSF for 3 days and treated with RANKL. WE extracted total RNA and analyzed by DNA microarray.
2009-09-05 | E-GEOD-17563 | biostudies-arrayexpress
Project description:Purpose: Among the diverse cytokines involved in osteoclast differentiation, IL-3 has been shown to inhibit RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. In the present study, we demonstrate that IL-3 activation of STAT5 inhibits RANKL-induced osteoclastogenesis through the induction of Id genes. Methods: To investigate the effect of STAT5 on osteoclast differentiation and IL-3-mediated inhibition of osteoclast differentiation, bone marrow derived macrophages isolated from STAT5 wild-type (Stat5fl/fl) or STAT5 cKO (STAT5;MX1-Cre) were differentiated to osteoclast in the presence of M-CSF and RANKL with or without IL-3; and bone marrow derived macrophges from STAT5 wild-type and STAT5 cKO were overexpressed with PMX-FIG (control) or STAT5A1*6 (constitutively active form of STAT5A) and differentiated to osteoclast. To analyze bone phenotype, femurs and tibiae of 16 week-old STAT5 wild-type and STAT5 cKO were subjected to micro CT analysis and histomorphometry, respectively. Results: Overexpression of STAT5 inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate either expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting that STAT5 plays an important role in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated expression of the Id1 and Id2 genes, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Moreover, micro-computed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in STAT5 conditional knockout mice than in wild-type mice in a RANKL injection model. Conclusion: Taken together, our results suggest that STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis through Id gene expression. Examination of 4 different combination of osteoclast differentiation condition of bone marrow derived macrophages.
2016-08-03 | E-GEOD-76988 | biostudies-arrayexpress
Project description:Comparison of gene expression of the osteoclast precursor myeloid blast seeded on plastic and on bone, primed with M-CSF for 4 days and culture with M-CSF and RANKL for 1 day. Osteoclasts and macrophages share progenitors that must receive decisive lineage signals driving them into their respective differentiation routes. Macrophage colony stimulation factor M-CSF is a common factor; bone is likely the stimulus for osteoclast differentiation. To elucidate the effect of both, shared mouse bone marrow precursor myeloid blast was pre-cultured with M-CSF on plastic and on bone. M-CSF priming prior to stimulation with M-CSF and osteoclast differentiation factor RANKL resulted in a complete loss of osteoclastogenic potential without bone. This coincided with a steeply decreased expression of osteoclast genes TRACP and DC-STAMP, but an increased expression of the macrophage markers F4/80 and CD11b. Compellingly, M-CSF priming on bone accelerated the osteoclastogenic potential: M-CSF primed cells that had received only one day M-CSF and RANKL and were grown on bone already expressed an array of genes that are associated with osteoclast differentiation and these cells differentiated into osteoclasts within 2 days. This implies that adhesion to bone dictates the fate of osteoclast precursors. Common macrophage-osteoclast precursors may become insensitive to differentiate into osteoclasts and regain osteoclastogenesis when bound to bone or when in the vicinity of bone.
2014-06-02 | GSE58146 | GEO
Project description:We showed that the transcription factor Foxo3 played a specific role in the polarization of CD4+ T cells towards pathogenic Th1 cells producing both interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). To understand the molecular mechanisms whereby Foxo3 controls CD4+ T cell differentiation, unbiased analysis of genes differentially expressed in Foxo3-deficient vs. Foxo3-sufficient CD4+ T cells was achieved using both resting and activated CD4+ T cells obtained following 12 or 24 hours of stimulation with anti-CD3 mAbs.
2016-09-01 | GSE86287 | GEO