2020
Identification of a 22 bp DNA cis Element that Plays a Critical Role in Colony Stimulating Factor 1-Dependent Transcriptional Activation of the SPHK1 Gene
Yao GQ, Zhu M, Walker J, Insogna K. Identification of a 22 bp DNA cis Element that Plays a Critical Role in Colony Stimulating Factor 1-Dependent Transcriptional Activation of the SPHK1 Gene. Calcified Tissue International 2020, 107: 52-59. PMID: 32246175, PMCID: PMC7274855, DOI: 10.1007/s00223-020-00685-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCells, CulturedDNAFibroblastsMacrophage Colony-Stimulating FactorMicePhosphotransferases (Alcohol Group Acceptor)Transcription FactorsTranscription, GeneticTranscriptional ActivationConceptsColony stimulating factor 1Sphingosine kinase 1Bp fragmentSPHK1 promoterBp sequenceSphK1 geneDNA cis elementsProtein binding regionsSPHK1 gene expressionBp DNA fragmentStimulating factor 1Dual-luciferase reporterPutative DNATranscriptional activationTranscription factorsNuclear proteinsDNA sequencesCis elementsDNA bindingGene expressionPromoter activityDNA fragmentsKinase 1EMSAsProtein binding
2018
Associations among circulating colony-stimulating factor-1, estrogen, and bone mineral density in postmenopausal women
Haas AV, Cong E, Simpson CA, Sukumar N, Deng Y, Insogna KL. Associations among circulating colony-stimulating factor-1, estrogen, and bone mineral density in postmenopausal women. Menopause The Journal Of The North American Menopause Society 2018, 25: 197-201. PMID: 28816930, DOI: 10.1097/gme.0000000000000974.Peer-Reviewed Original ResearchMeSH KeywordsBone DensityEstrogen Replacement TherapyEstrogensFemaleFemur HeadFemur NeckHumansMacrophage Colony-Stimulating FactorMiddle AgedPostmenopauseRandomized Controlled Trials as TopicSpineConceptsBone mineral densityEstrogen-deficient womenMineral densityBone lossColony-stimulating factor-1Kronos Early Estrogen Prevention StudyPostmenopausal bone lossPlacebo-controlled studyOsteoclastic bone resorptionFactor 1CSF-1 levelsCSF-1Estrogen replacementEstrogen therapyPlacebo groupPostmenopausal womenCardiovascular endpointsSerum levelsFemoral neckBone resorptionPrevention StudyAncillary studiesTreatment groupsWomenSignificant correlation
2014
The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*
Yao C, Yao GQ, Sun BH, Zhang C, Tommasini SM, Insogna K. The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*. Journal Of Biological Chemistry 2014, 289: 6775-6790. PMID: 24394418, PMCID: PMC3945339, DOI: 10.1074/jbc.m113.499210.Peer-Reviewed Original Research
2010
Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity
Itokowa T, Zhu ML, Troiano N, Bian J, Kawano T, Insogna K. Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity. Calcified Tissue International 2010, 88: 75-86. PMID: 21110188, PMCID: PMC3155765, DOI: 10.1007/s00223-010-9435-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesBone DensityBone ResorptionCells, CulturedChemotaxisFemaleMacrophage Colony-Stimulating FactorMaleMiceMice, KnockoutOrgan SizeOsteoclastsRac GTP-Binding ProteinsConceptsTrabecular bone massBone massMature osteoclastsFemoral cortical thicknessTotal bone areaNumber of osteoclastsWild-type miceNormal tooth eruptionNumber of osteoblastsWild-type animalsBone resorptionCortical porosityActin ring formationCortical thicknessTooth eruptionOsteoclast functionResorptive activityDefective chemotaxisBone areaFemale animalsMiceOsteoclastsMigratory rateNormal sizeSignificant differences
2009
Targeted overexpression of the two colony-stimulating factor-1 isoforms in osteoblasts differentially affects bone loss in ovariectomized mice
Yao GQ, Wu JJ, Ovadia S, Troiano N, Sun BH, Insogna K. Targeted overexpression of the two colony-stimulating factor-1 isoforms in osteoblasts differentially affects bone loss in ovariectomized mice. AJP Endocrinology And Metabolism 2009, 296: e714-e720. PMID: 19141689, PMCID: PMC2670621, DOI: 10.1152/ajpendo.90631.2008.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Nonredundant functionsWild-type animalsTransgenic miceMembrane-bound isoformMCSF1Normal osteoclastogenesisCollagen promoterTransgenic expressionMajor isoformsIsoformsFactor 1Same genotypeOp phenotypeTargeted overexpressionOverexpressionOp miceOsteoblastsAnimalsPromoterMicePhenotypeFemale animalsAlphaIMale littermates
2006
Colony-Stimulating Factor-1 Increases Osteoclast Intracellular pH and Promotes Survival via the Electroneutral Na/HCO3 Cotransporter NBCn1
Bouyer P, Sakai H, Itokawa T, Kawano T, Fulton CM, Boron WF, Insogna KL. Colony-Stimulating Factor-1 Increases Osteoclast Intracellular pH and Promotes Survival via the Electroneutral Na/HCO3 Cotransporter NBCn1. Endocrinology 2006, 148: 831-840. PMID: 17068143, DOI: 10.1210/en.2006-0547.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAlkaliesAmilorideAnimalsBicarbonatesCarbon DioxideCaspase InhibitorsCell SeparationCell SurvivalCells, CulturedEnzyme InhibitorsHydrogen-Ion ConcentrationIntracellular FluidMacrolidesMacrophage Colony-Stimulating FactorMiceMice, Inbred StrainsOsteoclastsProtonsRatsSodiumSodium-Bicarbonate SymportersConceptsProlong osteoclast survivalOsteoclast-like cellsColony-stimulating factor-1Osteoclast survivalCotransporter NBCn1Survival of osteoclastsHCO3- cotransporter NBCn1Caspase-8Inhibition of apoptosisExtracellular sodiumPromotes SurvivalOsteoclastsRT-PCRCellular alkalinizationSurvivalFactor 1Caspase-3NBCn1Intracellular pHCell survivalElectroneutral Na/Block activationPresent studySame extentFirst evidenceActivated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts
Sakai H, Chen Y, Itokawa T, Yu KP, Zhu ML, Insogna K. Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts. Bone 2006, 39: 1290-1301. PMID: 16950670, DOI: 10.1016/j.bone.2006.06.012.Peer-Reviewed Original ResearchMeSH KeywordsActinsAndrostadienesAnimalsBiological Transport, ActiveCdc42 GTP-Binding ProteinCells, CulturedCytoskeletonEnzyme InhibitorsGuanosine TriphosphateHumansMacrophage Colony-Stimulating FactorMiceModels, BiologicalOsteoclastsPhosphoinositide-3 Kinase InhibitorsProtein BindingProto-Oncogene Proteins c-vavPseudopodiaRac GTP-Binding ProteinsRatsReceptor, Macrophage Colony-Stimulating FactorRecombinant ProteinsSignal TransductionWortmanninConceptsCSF-1GEF activityCytoskeletal remodelingGTPase activityAssociation of VavC-fmsRac GTPase activityDominant negative Cdc42Dominant-negative RacCSF-1 receptorInhibitors of PI3CSF-1 treatmentTarget GTPaseActive RacExchange factorActive Cdc42Actin reorganizationLamellipodia formationPhosphotyrosine contentC-SrcPlasma membraneInhibitor of RhoARapid translocationVavRac translocation
2005
The Cell-Surface Isoform of Colony Stimulating Factor 1 (CSF1) Restores but Does Not Completely Normalize Fecundity in CSF1-Deficient Mice1
Ovadia S, Insogna K, Yao GQ. The Cell-Surface Isoform of Colony Stimulating Factor 1 (CSF1) Restores but Does Not Completely Normalize Fecundity in CSF1-Deficient Mice1. Biology Of Reproduction 2005, 74: 331-336. PMID: 16237150, DOI: 10.1095/biolreprod.105.045047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneFemaleFertilityLungMacrophage Colony-Stimulating FactorMaleMiceMice, TransgenicOsteoporosisPregnancyProtein IsoformsSpermatozoaUterusConceptsColony stimulating factor 1Viability of offspringReproductive defectsCell surfaceMembrane-bound isoformStimulating factor 1Cell surface isoformAlpha promoterMCSF1Transgenic animalsProteolytic sheddingCSF1 proteinMouse reproductionFactor 1ReproductionTransgenic male miceIsoformsTransgenic miceSperm numberOffspringTissue levelsMurine uterusGenetic absenceControl littermatesPromoterCSF-1 Induces fos Gene Transcription and Activates the Transcription Factor Elk-1 in Mature Osteoclasts
Yao G, Itokawa T, Paliwal I, Insogna K. CSF-1 Induces fos Gene Transcription and Activates the Transcription Factor Elk-1 in Mature Osteoclasts. Calcified Tissue International 2005, 76: 371-378. PMID: 15812575, DOI: 10.1007/s00223-004-0099-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell NucleusCells, CulturedDNA-Binding ProteinsEts-Domain Protein Elk-1Genes, fosMacrophage Colony-Stimulating FactorMiceMice, TransgenicOsteoclastsProto-Oncogene ProteinsProto-Oncogene Proteins c-fosRNA, MessengerTranscription FactorsTranscription, GeneticTranscriptional ActivationConceptsTranscription factor Elk-1Serum response elementTranscriptional activationElk-1CSF-1Response elementMature osteoclastsNuclear c-Fos proteinRegulation of FosBacterial lac Z geneC-fosSap-1aFos serum response elementFos promoterNuclear proteinsGene transcriptionFos geneMolecular mechanismsLac Z geneVehicle-treated cellsTargeted deletionFactor 1Absolute requirementC-Fos proteinLike cells
2003
The Cell Surface Form of Colony-Stimulating Factor-1 Is Biologically Active in Bone in Vivo
Yao GQ, Wu JJ, Sun BH, Troiano N, Mitnick MA, Insogna K. The Cell Surface Form of Colony-Stimulating Factor-1 Is Biologically Active in Bone in Vivo. Endocrinology 2003, 144: 3677-3682. PMID: 12865350, DOI: 10.1210/en.2002-221071.Peer-Reviewed Original ResearchConceptsOp/op miceWild-type miceOp miceBone densityTooth eruptionTransgenic micePeripheral quantitative computed tomographyMCSF-1Factor 1Number of osteoclastsQuantitative computed tomographyOp/op animalsMolar tooth eruptionWild-type animalsOP animalsComputed tomographyColony-stimulating factor-1Colony stimulating factor 1Normal incisorsHistomorphometric analysis
2002
A Role for Cell-Surface CSF-1 in Osteoblast-mediated Osteoclastogenesis
Yao G, Sun BH, Weir EC, Insogna KL. A Role for Cell-Surface CSF-1 in Osteoblast-mediated Osteoclastogenesis. Calcified Tissue International 2002, 70: 339-346. PMID: 12004339, DOI: 10.1007/s00223-001-1079-x.Peer-Reviewed Original ResearchAnimalsCell DifferentiationCell MembraneCells, CulturedFemaleMacrophage Colony-Stimulating FactorMaleMiceOligonucleotides, AntisenseOsteoblastsOsteoclastsStem Cells
2000
Nuclear Factor-κB p50 Is Required for Tumor Necrosis Factor-α-Induced Colony-Stimulating Factor-1 Gene Expression in Osteoblasts*
Yao G, Sun B, Insogna K, Weir E. Nuclear Factor-κB p50 Is Required for Tumor Necrosis Factor-α-Induced Colony-Stimulating Factor-1 Gene Expression in Osteoblasts*. Endocrinology 2000, 141: 2914-2922. PMID: 10919279, DOI: 10.1210/endo.141.8.7592.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesGene ExpressionHumansImmune SeraMacrophage Colony-Stimulating FactorMiceMice, KnockoutNF-kappa BOsteoblastsPromoter Regions, GeneticRNA, MessengerTumor Necrosis Factor-alphaConceptsCSF-1 expressionGene expressionElectrophoretic mobility shift assaysCSF-1 promoterCSF-1 gene expressionMobility shift assaysInducible complexTranscriptional mechanismsShift assaysNuclear factor-κB p50Northern analysisNF-kappaB p50NF-kappaB siteCSF-1Messenger RNAC-RelBcl-3Rel BRNA expressionTNF treatmentHematopoietic growth factorsMessenger RNA expressionIkappaB-alphaOsteoblastsNF-kappaBEvidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1.
Grey A, Chen Y, Paliwal I, Carlberg K, Insogna K. Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1. Endocrinology 2000, 141: 2129-38. PMID: 10830300, DOI: 10.1210/endo.141.6.7480.Peer-Reviewed Original ResearchAndrostadienesAnimalsBinding SitesCell MovementChromonesEnzyme InhibitorsImmunosorbent TechniquesMacrophage Colony-Stimulating FactorMiceMorpholinesOsteoclastsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProlineProto-Oncogene Proteins pp60(c-src)RatsReceptor, Macrophage Colony-Stimulating FactorRegulatory Sequences, Nucleic AcidSrc Homology DomainsWortmannin
1998
The Cell-surface Form of Colony-stimulating Factor-1 Is Regulated by Osteotropic Agents and Supports Formation of Multinucleated Osteoclast-like Cells*
Yao G, Sun B, Hammond E, Spencer E, Horowitz M, Insogna K, Weir E. The Cell-surface Form of Colony-stimulating Factor-1 Is Regulated by Osteotropic Agents and Supports Formation of Multinucleated Osteoclast-like Cells*. Journal Of Biological Chemistry 1998, 273: 4119-4128. PMID: 9461606, DOI: 10.1074/jbc.273.7.4119.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Osteoclast formationReverse transcriptase-polymerase chain reactionFactor 1Quantitative reverse transcriptase-polymerase chain reactionTumor necrosis factorTranscriptase-polymerase chain reactionOsteoclast-like cellsHematopoietic growth factorsCSF-1 isoformsView of evidenceCell surface formPolymerase chain reactionCo-culture systemNecrosis factorOsteotropic hormonesOsteoclast function
1997
Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts.
Insogna KL, Sahni M, Grey AB, Tanaka S, Horne WC, Neff L, Mitnick M, Levy JB, Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. Journal Of Clinical Investigation 1997, 100: 2476-2485. PMID: 9366562, PMCID: PMC508448, DOI: 10.1172/jci119790.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, NewbornCell MovementCells, CulturedCytoskeletonKineticsMacrophage Colony-Stimulating FactorMolecular Sequence DataOsteoclastsPeptidesPhosphoproteinsPhosphorylationPhosphotyrosinePolymerase Chain ReactionProto-Oncogene Proteins pp60(c-src)RatsSrc-Family KinasesSubstrate SpecificityConceptsColony-stimulating factor-1CSF-1 treatmentC-SrcC-fmsCellular proteinsC-Src-dependent tyrosine phosphorylationGrb2-binding proteinSrc kinase activityFactor 1Normal cytoskeletal architectureCytoskeletal architectureSrc geneCytoskeletal reorganizationTyrosine phosphorylationKinase activityPhosphotyrosine stainingCellular eventsF-actinActin distributionTargeted disruptionProteinRapid cytoplasmicLike cellsPhosphorylationOsteoclast-like cellsRole of c‐Src in cellular events associated with colony‐stimulating factor‐1‐induced spreading in osteoclasts
Insogna K, Tanaka S, Neff L, Horne W, Levy J, Baron R. Role of c‐Src in cellular events associated with colony‐stimulating factor‐1‐induced spreading in osteoclasts. Molecular Reproduction And Development 1997, 46: 104-108. PMID: 8981371, DOI: 10.1002/(sici)1098-2795(199701)46:1<104::aid-mrd16>3.0.co;2-2.BooksMeSH KeywordsActininAnimalsBone MarrowBone Marrow CellsCalcitriolCell SizeCells, CulturedCytoskeletonFemaleHumansMacrophage Colony-Stimulating FactorMiceMicroscopy, ConfocalOsteoblastsOsteoclastsOsteoporosisPhosphatidylinositol 4,5-DiphosphatePhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins pp60(c-src)RatsSignal TransductionConceptsOsteoclast-like cellsNeonatal rat osteoclastsRat osteoclastsCSF-1 treatmentMonoclonal antibodiesC-fmsCSF-1C-SrcCellular eventsWestern blot analysisTime-dependent increaseMurine bone marrowBasal abnormalitiesBone marrowConfocal microscopic studiesPIP2 contentSignificant doseReceptor tyrosine kinasesOsteoclastsTyrosine kinase activityC-Src kinase activityCell-signaling eventsTargeted disruptionTreatmentIntrinsic tyrosine kinase activity
1996
Colony stimulating factor‐1 plays a role in osteoclast formation and function in bone resorption induced by parathyroid hormone and parathyroid hormone‐related protein
Weir E, Lowik C, Paliwal I, Insogna K. Colony stimulating factor‐1 plays a role in osteoclast formation and function in bone resorption induced by parathyroid hormone and parathyroid hormone‐related protein. Journal Of Bone And Mineral Research 1996, 11: 1474-1481. PMID: 8889847, DOI: 10.1002/jbmr.5650111014.Peer-Reviewed Original ResearchConceptsBone resorptionMature osteoclastsParathyroid hormoneOsteoclast precursorsFetal rat long bonesParathyroid hormone-related proteinResistant acid phosphatase-positive osteoclastsMitogenic activityFactor 1Hormone-related proteinOrgan cultureCSF-1Rat long bonesTreatment of boneSignificant increaseOrgan culture assayHistological examinationBone assayOsteoclast recruitmentOsteoclast formationRat osteoclastsColony stimulating factor 1CSF-1 productionPTHResorptionTumor necrosis factor‐α induces transcription of the colony‐stimulating factor‐1 gene in murine osteoblasts
Kaplan D, Eielson C, Horowitz M, Insogna K, Weir E. Tumor necrosis factor‐α induces transcription of the colony‐stimulating factor‐1 gene in murine osteoblasts. Journal Of Cellular Physiology 1996, 168: 199-208. PMID: 8647916, DOI: 10.1002/(sici)1097-4652(199607)168:1<199::aid-jcp24>3.0.co;2-1.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1CSF-1 expressionMC3T3-E1 cellsCSF-1 mRNACSF-1 gene transcriptionMRNA stability studiesFactor 1 geneNew protein synthesisSecond messenger pathwaysPrimary mouse osteoblastsColony-stimulating factor-1 (CSF-1) geneTranscriptional mechanismsGene transcriptionResponsive cell linesInduces transcriptionNorthern analysisProgenitor proliferationTNF-alpha treatmentProtein synthesisCAMP pathwayTranscript expressionMessenger pathwaysMurine osteoblastsCycloheximide treatmentCellular mechanisms
1993
Macrophage colony‐stimulating factor release and receptor expression in bone cells
Weir E, Horowitz M, Baron R, Centrella M, Kacinski B, Insogna K. Macrophage colony‐stimulating factor release and receptor expression in bone cells. Journal Of Bone And Mineral Research 1993, 8: 1507-1518. PMID: 8304053, DOI: 10.1002/jbmr.5650081214.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone MarrowBone Marrow CellsCell DivisionCells, CulturedColony-Forming Units AssayCulture Media, ConditionedGranulocyte-Macrophage Colony-Stimulating FactorMacrophage Colony-Stimulating FactorMacrophagesMaleOsteoblastsOsteoclastsParathyroid HormoneParathyroid Hormone-Related ProteinProteinsRatsRats, Sprague-DawleyRats, WistarReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedConceptsColony-stimulating factorColony-stimulating activityM-CSFBone resorptionReceptor expressionMature osteoclastsPreincubation of CMColony-stimulating factor releaseHormone-related peptideM-CSF receptor c-FmsMacrophage colony-stimulating factorOsteoblast-osteoclast interactionsM-CSF mRNA levelsBone marrow cellsCSF-1 receptor expressionRat bone marrow cellsReceptor c-fmsROS 17/2.8 cellsParacrine roleImmunohistochemical techniquesRat osteoblastsPTHrP treatmentMarrow cellsFactor releasePTH