2014
Duodenal Absorption and Tissue Utilization of Dietary Heme and Nonheme Iron Differ in Rats
Cao C, Thomas CE, Insogna KL, O'Brien KO. Duodenal Absorption and Tissue Utilization of Dietary Heme and Nonheme Iron Differ in Rats. Journal Of Nutrition 2014, 144: 1710-1717. PMID: 25332470, PMCID: PMC4195416, DOI: 10.3945/jn.114.197939.Peer-Reviewed Original ResearchConceptsNonheme iron absorptionDivalent metal transporter 1Tissue utilizationLiver hepcidinDietary hemeMale Sprague-Dawley ratsDuodenal iron transportersHeme iron absorptionSprague-Dawley ratsHepatic hepcidin expressionIron storage tissuesIron loadingElevated hepcidinIron intakeMetal transporter 1Duodenal absorptionIron dextranNonheme ironIron overloadRat modelHepcidin expressionHepatic hepcidinStable iron isotopesDuodenal expressionHepcidin
2013
Increasing dietary protein acutely augments intestinal iron transporter expression and significantly increases iron absorption in rats
Thomas CE, Gaffney‐Stomberg E, Sun B, O'Brien KO, Kerstetter JE, Insogna KL. Increasing dietary protein acutely augments intestinal iron transporter expression and significantly increases iron absorption in rats. The FASEB Journal 2013, 27: 2476-2483. PMID: 23447582, DOI: 10.1096/fj.12-221945.Peer-Reviewed Original ResearchConceptsIntestinal Fe absorptionDietary proteinFe absorptionIron transporter expressionTranscript expressionDuodenal mucosaAcute effectsSprague-DawleyStable iron isotopesIron absorptionShort-term effectsIsocaloric dietsIron deficiencyTransporter expressionLittle dataTransferrin receptorExpression of genesSeparate studiesGroupCurrent studyBalance studiesExpressionWhole genome profilingDawleyMucosa
2010
Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice
Yao GQ, Wu JJ, Troiano N, Insogna K. Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice. Journal Of Bone And Mineral Metabolism 2010, 29: 141-148. PMID: 20602130, PMCID: PMC3457021, DOI: 10.1007/s00774-010-0202-3.Peer-Reviewed Original ResearchConceptsParathyroid hormonePTH treatmentBone massTg miceAnabolic responseDKK1 expressionSingle daily subcutaneous doseDaily subcutaneous doseBone formationIntermittent PTH treatmentPotent anabolic agentOverexpression of DKK1Number of osteoblastsSubcutaneous doseWT miceReal-time PCRSkeletal sitesDickkopf-1Anabolic agentsBody weightTransgenic miceHistomorphometric parametersHistomorphometric analysisTargeted overexpressionPrimary murine osteoblastsThe Effect of Dietary Protein on Intestinal Calcium Absorption in Rats
Gaffney-Stomberg E, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL. The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats. Endocrinology 2010, 151: 1071-1078. PMID: 20147526, PMCID: PMC2840679, DOI: 10.1210/en.2009-0744.Peer-Reviewed Original ResearchConceptsIntestinal Ca absorptionCa absorptionHigh-protein dietUrinary calciumBrush border membrane vesiclesProtein intakeFemale Sprague-Dawley ratsProtein dietProtein intake resultsIntestinal calcium absorptionDietary protein intakeHigh protein intakeSprague-Dawley ratsLow-protein groupHigh protein groupDietary protein effectsCalcium absorptionAcute increaseDawley ratsDuodenal mucosaIntake resultsRatsCa balanceTranscellular CaDietary protein
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
l-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells
Busque SM, Kerstetter JE, Geibel JP, Insogna K. l-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. AJP Gastrointestinal And Liver Physiology 2005, 289: g664-g669. PMID: 15961860, DOI: 10.1152/ajpgi.00096.2005.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorAbsence of secretagoguesAcid secretionParietal cellsHistamine-2 receptorSystem L amino acid transportGastric acid secretionWhole stomach preparationDose-dependent increaseIndividual parietal cellsStomach preparationRat gastric glandsHEK-293 cellsCaSRL-amino acidsGastric glandsHormonal stimulationATPase activitySecretionPhysiological concentrationsReceptorsSecretagoguesAcid transportAmino acidsSecretory cellsMultiple melanocortin receptors are expressed in bone cells
Zhong Q, Sridhar S, Ruan L, Ding KH, Xie D, Insogna K, Kang B, Xu J, Bollag RJ, Isales CM. Multiple melanocortin receptors are expressed in bone cells. Bone 2005, 36: 820-831. PMID: 15804492, DOI: 10.1016/j.bone.2005.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneAnimalsBase SequenceBlotting, NorthernBlotting, SouthernCyclic AMPDNA PrimersHumansImmunohistochemistryMiceOligonucleotide Array Sequence AnalysisOsteoblastsPro-OpiomelanocortinProtein BindingRatsReceptors, CorticotropinReceptors, MelanocortinReverse Transcriptase Polymerase Chain ReactionRNA, MessengerThymidineConceptsMelanocortin receptorsBone turnoverOsteoclastic cellsReceptor familySteroid hormone secretionBone cellsMelanocortin receptor familyFamily of receptorsHormone secretionBeta-endorphinSpecific effectsPOMC fragmentsPOMC mRNACell subpopulationsAlpha betaGamma-MSHReceptorsPeptide hormonesPOMCG proteinsVivo dataBoneHormoneOsteoblastic cellsVariety of genes
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
2001
IL-6 negatively regulates IL-11 production in vitro and in vivo.
Nakchbandi I, Mitnick M, Masiukiewicz U, Sun B, Insogna K. IL-6 negatively regulates IL-11 production in vitro and in vivo. Endocrinology 2001, 142: 3850-6. PMID: 11517162, DOI: 10.1210/endo.142.9.8368.Peer-Reviewed Original ResearchConceptsIL-11 productionIL-6IL-11Bone resorptionOsteoclast formationIL-6 levelsIL-11 levelsFive-day infusionPTH excessPrimary hyperparathyroidismSerum levelsResorptive responseParathyroid adenomectomyPretreatment of cellsHuman PTHNonimmune serumPTHEffect of pretreatmentMRNA levelsSteady-state mRNA levelsPatientsCytokinesHuman osteoblast-like cellsResorptionSaos-2 cellsParathyroid 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
Evidence 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
1999
A Role for Interleukin-6 in Parathyroid Hormone-Induced Bone Resorption in Vivo
Grey A, Mitnick M, Masiukiewicz U, Sun B, Rudikoff S, Jilka R, Manolagas S, Insogna K. A Role for Interleukin-6 in Parathyroid Hormone-Induced Bone Resorption in Vivo. Endocrinology 1999, 140: 4683-4690. PMID: 10499526, DOI: 10.1210/endo.140.10.7036.Peer-Reviewed Original ResearchConceptsParathyroid hormoneInterleukin-6Bone resorptionBiochemical markersPTH infusionEffect of PTHIL-6 productionCytokine interleukin-6Bone-resorbing cellsRelease of calciumPrimary hyperparathyroidismSerum levelsOsteoblastic cellsParacrine agentsCalcium homeostasisExperimental animalsPermissive roleChronic deficiencyResorptionImportant mediatorSystemic levelsBone formationRegulatory effectsInfusionMarkers
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 cellsParathyroid Hormone Increases Circulating Levels of Fibronectin in Vivo: Modulating Effect of Ovariectomy
Sun B, Mitnick M, Eielson C, Yao G, Paliwal I, Insogna K. Parathyroid Hormone Increases Circulating Levels of Fibronectin in Vivo: Modulating Effect of Ovariectomy. Endocrinology 1997, 138: 3918-3924. PMID: 9275082, DOI: 10.1210/endo.138.9.5421.Peer-Reviewed Original ResearchConceptsLevels of fibronectinEffect of PTHAbility of PTHHuman PTHAdult female Sprague-Dawley ratsFemale Sprague-Dawley ratsCultured fetal rat bonesDiminished bone formationEstrogen-deficient stateHuman PTH-(1-34) infusionSprague-Dawley ratsFN productionFetal rat boneBisphosphonate APDHPTH groupPTH infusionCirculating LevelsAlzet minipumpsEstrogen deficiencyParathyroid hormoneEstrogen withdrawalBone resorptionAnabolic propertiesROS 17/2.8 cellsEffective agonistRole 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 productionPTHResorptionEffects of continuous glucocorticoid infusion on bone metabolism in the rat
King CS, Weir EC, Gundberg CW, Fox J, Insogna KL. Effects of continuous glucocorticoid infusion on bone metabolism in the rat. Calcified Tissue International 1996, 59: 184-191. PMID: 8694896, DOI: 10.1007/s002239900107.Peer-Reviewed Original ResearchConceptsDEX treatmentBone metabolismUrinary calcium/creatinine ratioCalcium/creatinine ratioIntact parathyroid functionLevels of PTHSprague-Dawley ratsTartrate-resistant acid phosphataseParathyroid functionTime-dependent mannerCreatinine ratioSerum calciumBone turnoverContinuous administrationParathyroidectomized animalsSerum concentrationsSupraphysiologic dosesGlucocorticoid infusionDawley ratsFemoral weightHistomorphometric findingsBone massPTX animalsBone volumeDexamethasone
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