2021
Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen
Zhu M, Sun BH, Nevius E, Kaplan J, Pereira J, Insogna K. Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen. PLOS ONE 2021, 16: e0247199. PMID: 33607650, PMCID: PMC7895546, DOI: 10.1371/journal.pone.0247199.Peer-Reviewed Original ResearchConceptsColony stimulating factor 1Mature osteoclastsBone massHigh bone mass phenotypeAttenuated anabolic responseDaily subcutaneous dosesTrabecular bone massBone mass phenotypeC-fmsNormal tooth eruptionTrabecular bone compartmentsMature osteoclast functionCathepsin K promoterFemurs of maleWild-type animalsOcS/BSFemale knockSubcutaneous dosesNormal weightSmall osteoclastsImpaired responseTrabecular numberAnabolic responseFlox miceMass phenotype
2017
Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo
Yao C, Yu KP, Philbrick W, Sun BH, Simpson C, Zhang C, Insogna K. Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. International Journal Of Molecular Medicine 2017, 40: 1067-1077. PMID: 28791343, PMCID: PMC5593463, DOI: 10.3892/ijmm.2017.3091.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBone ResorptionCathepsin KCell LineFemaleFemurFibroblastsGene Expression RegulationHEK293 CellsHeLa CellsHumansMaleMiceMice, Inbred C57BLMice, TransgenicNeuropeptidesNF-kappa BOrgan SpecificityOsteoclastsPromoter Regions, GeneticRac1 GTP-Binding ProteinRANK LigandSignal TransductionTibiaConceptsNF-κB signalingCell type-dependent roleCritical downstream targetNF-κBCanonical NF-κB signalingNuclear factorReceptor activatorNuclear Rac1Adaptor proteinCancer-associated genesMature osteoclast formationSmall GTPaseDownstream targetsExogenous receptor activatorLow-dose RANKLNF-κB interactionTransgenic animalsImportant regulatorBreast cancer-associated genesWild-type littermatesCell typesRac1SignalingBCA3Dependent role
2016
Hypophosphatemia promotes lower rates of muscle ATP synthesis
Pesta DH, Tsirigotis DN, Befroy DE, Caballero D, Jurczak MJ, Rahimi Y, Cline GW, Dufour S, Birkenfeld AL, Rothman DL, Carpenter TO, Insogna K, Petersen KF, Bergwitz C, Shulman GI. Hypophosphatemia promotes lower rates of muscle ATP synthesis. The FASEB Journal 2016, 30: 3378-3387. PMID: 27338702, PMCID: PMC5024687, DOI: 10.1096/fj.201600473r.Peer-Reviewed Original ResearchConceptsMuscle ATP synthesisATP synthesisMuscle weaknessIsolated muscle mitochondriaSolute carrier familyWild-type littermate controlsSolute carrier family 34Carrier familyLower ratesInsulin-stimulated ratesMuscle mitochondriaChronic hypophosphatemiaHeart failureHypophosphatemic groupHypophosphatemic miceHypophosphatemiaLittermate controlsKnockout miceBlood PLow ratePlasma PPatientsSimilar findingsMember 1Plasma inorganic phosphate
2009
Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice
Liang G, Katz LD, Insogna KL, Carpenter TO, Macica CM. Survey of the Enthesopathy of X-Linked Hypophosphatemia and Its Characterization in Hyp Mice. Calcified Tissue International 2009, 85: 235-246. PMID: 19609735, PMCID: PMC2988401, DOI: 10.1007/s00223-009-9270-6.Peer-Reviewed Original ResearchMeSH KeywordsAchilles TendonAdolescentAdultAgedAnimalsBiomarkersCalcinosisChildDisease Models, AnimalDisease ProgressionFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGenetic Diseases, X-LinkedHumansMiceMice, Inbred C57BLMiddle AgedPatellar LigamentPhenotypeQuadriceps MuscleRadiographyRheumatic DiseasesTendinopathyTendonsYoung AdultConceptsFGF-23Fibroblast growth factor receptor 3Hyp miceMajority of patientsHigh circulating levelsPhosphate-regulating hormoneBone spur formationTendon insertion siteGrowth factor receptor 3Insertion siteLigament insertion sitesCirculating LevelsPhosphate excretionBone-forming osteoblastsHeterotopic calcificationOsteophyte formationHistological examinationMurine modelReceptor 3Spur formationHypophosphatemiaEnthesis fibrocartilageBone mineralizationBiochemical milieuMiceTargeted 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
2008
The Anabolic Response to Parathyroid Hormone Is Augmented in Rac2 Knockout Mice
Kawano T, Troiano N, Adams DJ, Wu JJ, Sun BH, Insogna K. The Anabolic Response to Parathyroid Hormone Is Augmented in Rac2 Knockout Mice. Endocrinology 2008, 149: 4009-4015. PMID: 18467443, PMCID: PMC2488220, DOI: 10.1210/en.2008-0034.Peer-Reviewed Original ResearchConceptsAnabolic responseType 1 collagenWild-type animalsPTH treatmentKnockout miceResorptive activityAvailable anabolic therapyTotal bone densityAge-matched wild-type animalsSerum aminoterminal propeptideWild-type groupRac2 knockout miceGroups of animalsAnabolic therapyParathyroid hormoneResorptive responseSerum markersOsteoclast numberTherapeutic responseAminoterminal propeptideBone massBone densitySkeletal responseCortical thicknessGenetic absenceImpact of Glucose‐Dependent Insulinotropic Peptide on Age‐Induced Bone Loss*
Ding K, Shi X, Zhong Q, Kang B, Xie D, Bollag WB, Bollag RJ, Hill W, Washington W, Mi Q, Insogna K, Chutkan N, Hamrick M, Isales CM. Impact of Glucose‐Dependent Insulinotropic Peptide on Age‐Induced Bone Loss*. Journal Of Bone And Mineral Research 2008, 23: 536-543. PMID: 18072880, PMCID: PMC2669161, DOI: 10.1359/jbmr.071202.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsGastric Inhibitory PolypeptideGlucoseMaleMiceMice, Inbred C57BLMice, TransgenicOsteoporosisConceptsGlucose-dependent insulinotropic peptideAge-induced bone lossBone marrow stromal cellsGIP receptor expressionBone lossBone massMo of ageGIP effectsInsulinotropic peptideReceptor expressionEffects of GIPBone strengthOsteoblastic activityAge-associated bone lossElevated GIP levelsFunctional GIP receptorsWildtype control miceBone histomorphometric dataC57BL/6 transgenic miceAge-dependent fashionAge-related decreaseAge-related lossDifferentiation of BMSCsAge-dependent mannerAge-related changes
2007
Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass
Xie D, Zhong Q, Ding KH, Cheng H, Williams S, Correa D, Bollag WB, Bollag RJ, Insogna K, Troiano N, Coady C, Hamrick M, Isales CM. Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass. Bone 2007, 40: 1352-1360. PMID: 17321229, DOI: 10.1016/j.bone.2007.01.007.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic peptideBone massGIP receptorBone resorptionBone formationNutrient ingestionTransgenic miceGIP receptor knockout miceLow bone mass phenotypeReceptor knockout miceBone mass phenotypeSignificant increaseCollagen type I synthesisGIP levelsInsulinotropic peptideAnabolic hormonesOsteoclastic activityMouse modelDietary zincMass phenotypeKnockout miceReceptor signalingReceptors resultsMiceHormone
2006
Effects 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 transcripts
2004
The Effect of Aging on the Skeletal Response to Intermittent Treatment with Parathyroid Hormone
Knopp E, Troiano N, Bouxsein M, Sun BH, Lostritto K, Gundberg C, Dziura J, Insogna K. The Effect of Aging on the Skeletal Response to Intermittent Treatment with Parathyroid Hormone. Endocrinology 2004, 146: 1983-1990. PMID: 15618351, DOI: 10.1210/en.2004-0770.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBone and BonesBone DensityBone RemodelingMaleMiceMice, Inbred C57BLOsteoblastsParathyroid HormoneStem CellsConceptsBody bone mineral densitySkeletal responseAged animalsIntermittent treatmentTotal body bone mineral densityYoung adult C57BL/6 miceDaily sc injectionsVehicle-treated animalsTrabecular bone volume fractionYoung adult miceBone mineral densityYoung adult animalsVertebral histomorphometryEffect of ageBone volume fractionParathyroid hormoneC57BL/6 miceSC injectionPTH treatmentMineral densityBody weightOsteoblast numberPTHCultured marrowYounger counterparts
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