Mus musculus
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ABSTRACT:
PROVIDER: PRJNA99829 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice
2007-06-01 | GSE7798 | GEO
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Experiment Overall Design: Wild type and osteoclast-specific Estrogen Receptor alpha knock-out mice were ovariectomized. The number of both genotypes of mice was eight. The mice of each genotypes were divided to vehicle control and estrogen treated group. Four hours after chemical treatment, the distal 5 mm of the left femurs were harvested after sacrificing by cervical dislocation and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling. Therefore, this experiment consists of four groups with four replicates per group.
2008-06-15 | E-GEOD-7798 | biostudies-arrayexpress
Project description:Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive breast cancer (BC) and is the primary target of specific anticancer therapies that although effective can generate resistance phenomena that represents a crucial problem in clinical management of patients affected by this disease. DOT1 Like Histone Lysine Methyltransferase (DOT1L) and Menin 1 (MEN1) have been identified as functional component of the ERα mechanism of action. To investigate the involvement of DOT1L and MEN1 in mediating ERα actions in hormone-responsive and endocrine-resistant BC, interaction proteomics was applied to map the DOT1l and MEN1 nuclear interacting partners in MCF7 breast cancer cell nuclei in order to the identifiy new possible therapeutic targets for a more effective pharmacological treatment of endocrine therapy-resistant tumors.
2022-08-12 | PXD026864 | Pride
Project description:Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive breast cancer (BC) and is the primary target of specific anticancer therapies. Although ERα blockade with these drugs is effective, the development of a resistance to treatment represents the key problem in clinical management of patients affected by this disease. Understanding the molecular mechanisms underlying ERα action in BC cells may help the identification of new therapeutic targets for more effective pharmacological treatment of endocrine therapy-resistant tumors. We recently discovered the epigenetic enzyme DOT1L (DOT1 Like Histone Lysine Methyltransferase) as a novel nuclear partner of ERα in BC cells. To investigate the involvement of DOT1L in mediating ERα actions in hormone-responsive and endocrine-resistant BC, physical and functional interaction between these two molecules on chromatin was mapped by Chromatin Immunoprecipitation coupled to Mass Spectrometry (ChIP-MS).
2019-02-09 | PXD010314 | Pride
Project description:Healthy alveolar bone is the cornerstone for oral function and oral treatment. In the aging population, increasingly postmenopausal women requiring dental services experiences alveolar bone loss due to estrogen deficiency. Both local factors (occlusal force lose) and systemic factors (estrogen deficiency) affects their alveolar bone health, but the association remains to be clarified. Here, we identified that occlusal force is critical in maintaining alveolar bone mass and PIEZO1 coordinates mechanical force and estrogen, thus orchestrating alveolar bone homeostasis. Mechanistically, both occlusal force loss and PIEZO1 deletion may impair the osteogenesis of alveolar bone and sequentially regulate catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. PIEZO1 may promote the activity of signal transducer and activator of transcription 3 (STAT3) and estrogen receptor 1 (ESR1), which cooperatively increase Fasl transcription. This study thus revealed a cooperation between occlusal force and estrogen in maintaining alveolar bone homeostasis through a PIEZO1-STAT3/ESR1-FasL pathway. Our work supports restoration of occlusal force with dental therapies early and suggests that preventing alveolar bone loss is the major priority. PIEZO1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.
2025-12-31 | GSE205377 | GEO
Project description:The Estrogen Receptor alpha (ERα), is a member of the nuclear receptor superfamily of trancriptional regulators that mediates estrogen signaling in hormone-responsive tumors controlling key cellular functions by assembling in large functional multiprotein complexes. Interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors partners whom association with the receptor is mediated by RNAs
2019-07-29 | PXD012630 | Pride
Project description:Active estrogen receptor-alpha signaling in ovarian cancer
| PRJNA322076 | ENA
Project description:Fas ligand (FasL)/TNFSF6, a member of the tumor necrosis factor (TNF) superfamily, can promote apoptosis in activated primary B cells, T cells, dendritic cells, and synovial fibroblasts through Fas and is involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble FasL in addition to TL1A and LIGHT and inhibits the signaling of FasL via Fas. Therefore, FasL-DcR3/Fas signaling may be involved in the pathogenesis of RA. We hypothesized that FasL regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by FasL.
2020-06-30 | GSE153378 | GEO
Project description:Estrogen receptor alpha (ERα) is a ligand dependent transcription regulator, which contains two transactivation functional domains, AF-1 and AF-2. These activities are regulated differently by the ligands. Specifically, the selective estrogen receptor modulators (SERMs) regulate AF-1 rather than AF-2. It is important to know whether AF-1/AF-2 predominantly regulated genes exist in the tissues for a better understanding of the SERMs functionality. We sought out AF-1 dependent estrogenic genes by using the AF-2 mutated knock-in (KI) mouse model, AF2ERKI. AF2ER is an estrogen-insensitive AF-2 disrupted ERα mutant mouse but unique to this model, AF-1 can be activated by the estrogen-antagonists, such as fulvestrant (ICI) and 4-hydroxytamoxifen (Tam) in vitro and in vivo. The information of genome-wide ICI or Tam dependent AF-2 mutated ERα binding sites could explain the mechanism of the selective estrogenic action of SERMs through AF-1 dependent gene regulation.
2019-12-10 | GSE137196 | GEO
Project description:Estrogen Receptor Alpha Signaling in Cervical Cancer Associated Fibroblasts
| PRJNA273453 | ENA