grant
Antagonism of RANKL signaling by estrogen in osteoclasts
Organization UNIV OF ARKANSAS FOR MED SCISLocation LITTLE ROCK, UNITED STATESPosted 22 Mar 2024Deadline 28 Feb 2029
NIHUS FederalResearch GrantFY2026Adaptor ProteinAdaptor Protein GeneAdaptor Signaling ProteinAdaptor Signaling Protein GeneAllelesAllelomorphsApoptosisApoptosis PathwayApoptosis Regulator BAKApoptoticAquadiolAttenuatedB breveB cell lymphoma 2B-Cell CLL/Lymphoma 2 GeneB-cell lymphoma/leukemia-2B. breveBAX Isoform AlphaBCL2BCL2 geneBCL2-Antagonist/Killer 1BCL2-Associated X ProteinBacillus casei gBacillus gBax proteinBcl-2Bcl-2 Homologous Antagonist/KillerBetabacterium breveBindingBone MatrixBone ResorptionBone Resorption InhibitionCell BodyCell Communication and SignalingCell DeathCell Death Inhibitor 1Cell DifferentiationCell Differentiation processCell LineageCell SignalingCell fusionCellsCessation of lifeComplexDeathDevelopmentDimenformonDiogynDiogynetsERalphaERαESR1ESR1 geneEnzyme GeneEnzymesEstraceEstradiolEstradiol Receptor alphaEstradiol Receptor αEstradiol-17 betaEstradiol-17betaEstraldineEstrogen Receptor 1Estrogen Receptor alphaEstrogen Receptor αEstrogen declineEstrogen deficiencyEstrogensExperimental DesignsExpression SignatureFoundationsGene Expression ProfileGeneticGiant CellsHydrogen OxideImmune responseIn VitroInflammatoryIntermediary MetabolismIntracellular Communication and SignalingKnowledgeL breveL brevisL. breveL. brevisLactobacillus brevisLactobacterium breveMacrophageMeasuresMediatingMembraneMenopauseMetabolic ProcessesMetabolismMiceMice MammalsMicroscopyMitochondriaMolecularMolecular InteractionMultinucleated Giant CellsMurineMusMyelogenousMyeloidMyeloid CellsMyeloid ProgenitorMyeloid Progenitor CellsMyeloid Stem CellsMφNADHNADH oxidaseNR3A1OPGLOophorectomyOsteoclastic Bone LossOsteoclastsOsteoporosisOvariectomyOvocyclinOvocylinOxidation-ReductionPathway interactionsPolykaryocytesPopulationProcessProductionProgrammed Cell DeathProgynonProtein FamilyProteinsRANKLReceptor ProteinRedoxRegulationRespirationSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSkeletonSyncytiumTNF Receptor-Associated Factor 6 GeneTNFSF11TNFSF11 geneTRAF6TRAF6 geneTestingTherapeutic EstradiolTherapeutic EstrogenTimeTzanck CellWaterWorkadapter proteinantagonismantagonistattenuateattenuatesbak proteinbcl-2 Genesbcl-2 homologous antagonist-killer proteinbiological signal transductionbonebone lossbone massbone resorbing activityced9 homologcellular differentiationcytokinedecline in estrogendecrease estrogendecrease in estrogendeficiency in estrogendevelop therapydevelopmentaldiminished estrogenestrogen depletionestrogen level decreaseestrogen lossfemale gonadectomyfracture riskgene expression patterngene expression signaturehRANKL2host responseimmune system responseimmunoresponsein vivoinsightintervention developmentloss of functionmembermembrane structuremitochondrialmyeloid precursormyeloid stem and progenitor cellnecrocytosisnovelosteoclast progenitorosteoclastogenesisoverexpressoverexpressionoxidation reduction reactionpathwaypreventpreventingprogenitorreceptorrecruitreduced estrogenrespiratory mechanismresponsesOdfscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingskeletonstherapy developmenttooltranscriptional profiletranscriptional signaturetreatment development
Description preview
PROJECT SUMMARY/ABSTRACT
Loss of estrogens at menopause is a major cause of osteoporosis due to an increase in number and activity of
the cells that resorb bone called osteoclasts. Estrogens inhibit bone resorption in part via direct effects on
osteoclasts. However, the cellular and molecular mechanisms responsible for the direct effects of…
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