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 ResearchConceptsColony 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
2011
Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss
Yao GQ, Wu JJ, Troiano N, Zhu ML, Xiao XY, Insogna K. Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss. Journal Of Bone And Mineral Metabolism 2011, 30: 408-418. PMID: 22105655, PMCID: PMC4378684, DOI: 10.1007/s00774-011-0336-y.Peer-Reviewed Original ResearchAnimalsBone and BonesBone DensityCell DifferentiationCells, CulturedCoculture TechniquesColony-Stimulating FactorsFemaleHumansHypertriglyceridemiaMaleMiceMice, KnockoutOsteoblastsOsteoclastsOsteoporosisOsteoporosis, PostmenopausalProtein IsoformsRNA, MessengerSex CharacteristicsSolubilityUp-Regulation
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 ResearchConceptsTrabecular 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
2007
Breast Cancer–Associated Gene 3 (BCA3) Is a Novel Rac1‐Interacting Protein*
Yu K, Itokawa T, Zhu M, Syam S, Seth A, Insogna K. Breast Cancer–Associated Gene 3 (BCA3) Is a Novel Rac1‐Interacting Protein*. Journal Of Bone And Mineral Research 2007, 22: 628-637. PMID: 17227220, DOI: 10.1359/jbmr.070105.Peer-Reviewed Original Research
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 evidenceEffects of glucose-dependent insulinotropic peptide on osteoclast function
Zhong Q, Itokawa T, Sridhar S, Ding KH, Xie D, Kang B, Bollag WB, Bollag RJ, Hamrick M, Insogna K, Isales CM. Effects of glucose-dependent insulinotropic peptide on osteoclast function. AJP Endocrinology And Metabolism 2006, 292: e543-e548. PMID: 17003233, DOI: 10.1152/ajpendo.00364.2006.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic peptideBone resorptionNutrient ingestionGIP receptorOrgan culture systemBone breakdownEffects of GIPOsteoclast functionMature osteoclastsGlucose-induced insulin secretionGIP receptor transcriptsImmediate postprandial periodBone formationAnti-resorptive effectsGlucose-dependent insulinotropicIntestinal endocrine cellsOsteoclast resorptive activityPostprandial reductionIncretin hormonesInsulinotropic peptidePostprandial periodInsulin secretionResorptive activityOsteoclastic cellsReceptor transcriptsActivated 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
CSF-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
2004
LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1
Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, Xu T. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nature Cell Biology 2004, 6: 609-617. PMID: 15220930, DOI: 10.1038/ncb1140.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActomyosinAnimalsAnimals, NewbornAntibodiesCell CycleCell DivisionCells, CulturedDNA-Binding ProteinsFeedback, PhysiologicalFetusGiant CellsHeLa CellsHumansLim KinasesMiceMice, KnockoutMicrofilament ProteinsPhosphorylationPolymersProtein BindingProtein KinasesProtein Serine-Threonine KinasesRNA InterferenceConceptsTumor suppressorActomyosin contractile ringPhosphorylation of cofilinCytokinesis defectsCytoskeleton regulatorsAntibody microinjectionContractile ringActin polymerizationGene knockoutCytokinesisLIMK1LATS1Multinucleate cellsNegative modulationSuppressorDrosophilaCellsColocalizesCofilinMammals
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 Research
2001
Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor
Mitnick M, Grey A, Masiukiewicz U, Bartkiewicz M, Rios-Velez L, Friedman S, Xu L, Horowitz M, Insogna K. Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor. AJP Endocrinology And Metabolism 2001, 280: e405-e412. PMID: 11171594, DOI: 10.1152/ajpendo.2001.280.3.e405.Peer-Reviewed Original ResearchConceptsInterleukin-6IL-6sRParathyroid hormoneSoluble receptorBioactive interleukin-6Hepatic IL-6 productionBioactive IL-6IL-6 productionType 1 receptorHepatic stellate cellsDose-dependent productionIsolated rat liverHepatic endothelial cellsIL-6sR.Serum levelsBone resorptionHepatic productionEndocrine effectsKupffer cellsStellate cellsPTHImportant mediatorEndothelial cellsLiverHormone
2000
Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade
Nakchbandi I, Weir E, Insogna K, Philbrick W, Broadus A. Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 7296-7300. PMID: 10829073, PMCID: PMC16539, DOI: 10.1073/pnas.110553397.Peer-Reviewed Original ResearchConceptsNumber of osteoclastsEffects of PTHrPOsteoclast formationDF cellsBone resorptionFactor expressionOsteoclastic bone resorptionDental follicle cellsHormone-related proteinOsteoclast differentiation factorStellate reticulum cellsOsteoclastogenesis inhibitory factorCoronal tooth surfacesSpontaneous osteoclast formationParacrine cascadeParathyroid hormoneEruption pathwayReticulum cellsPeripheral skeletonTooth eruptionOsteoclast precursorsPTH/PTHrP.Inhibitory factorFunctional osteoclastsCrypt cells
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
Tumor 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
1994
Estrogen modulates parathyroid hormone-induced fibronectin production in human and rat osteoblast-like cells.
Eielson C, Kaplan D, Mitnick MA, Paliwal I, Insogna K. Estrogen modulates parathyroid hormone-induced fibronectin production in human and rat osteoblast-like cells. Endocrinology 1994, 135: 1639-44. PMID: 7925127, DOI: 10.1210/endo.135.4.7925127.Peer-Reviewed Original Research
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
1989
Parathyroid Hormone-Related Protein Modulates the Effect of Transforming Growth Factor-β on Deoxyribonucleic Acid and Collagen Synthesis in Fetal Rat Bone Cells*
CENTRELLA M, CANALIS E, MCCARTHY TL, STEWART AF, ORLOFF JJ, INSOGNA KL. Parathyroid Hormone-Related Protein Modulates the Effect of Transforming Growth Factor-β on Deoxyribonucleic Acid and Collagen Synthesis in Fetal Rat Bone Cells*. Endocrinology 1989, 125: 199-208. PMID: 2737143, DOI: 10.1210/endo-125-1-199.Peer-Reviewed Original Research
1988
Characterization of a parathyroid Hormonelike Peptide Secreted by Human Keratinocytes
INSOGNA K, STWART A, IKEDA K, CENTRELLA M, MILSONE L. Characterization of a parathyroid Hormonelike Peptide Secreted by Human Keratinocytes. Annals Of The New York Academy Of Sciences 1988, 548: 146-159. PMID: 2470290, DOI: 10.1111/j.1749-6632.1988.tb18801.x.Peer-Reviewed Original Research