2024
Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis
Zhu M, Zeiss C, Hamrick M, Weinstein R, Sun B, Brotto M, Liu X, Siu E, Huttner A, Tommasini S, Simpson C, Insogna K. Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis. Bone 2024, 184: 117086. PMID: 38552893, DOI: 10.1016/j.bone.2024.117086.Peer-Reviewed Original ResearchConceptsDeletion of Mfn2Bone mineral densityMitofusin 2Reduced expression of Mfn2Myofiber atrophySpinal cordTransgenic mice expressing CreMice expressing CreNon-redundant roleSkeletal muscle histologyLumbar spinal cordTrabecular bone massLean body massExpression of Mfn2Mitochondrial reticulumMFN2 geneDisruption of cellular architectureImpaired osteoblast differentiationOsteoblast lineage commitmentMfn2Mitochondrial sizeMitofusinMineral densityCo-expressionDisorganized sarcomeres
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
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 osteoblasts
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
2008
Impact 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
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 ResearchConceptsColony 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
2004
The expanding role of PI3-kinase in bone
Golden LH, Insogna KL. The expanding role of PI3-kinase in bone. Bone 2004, 34: 3-12. PMID: 14751558, DOI: 10.1016/j.bone.2003.09.005.BooksMeSH KeywordsAnimalsBone and BonesHumansMiceMice, TransgenicOsteoblastsPhosphatidylinositol 3-KinasesSignal TransductionConceptsRole of PI3PI3-KsC-fmsTyrosine kinase c-SrcKinase c-SrcDifferent substrate specificitiesCritical downstream effectorCell surface receptorsActin remodelingSignal transductionPI3-kinaseC-SrcSubstrate specificityDownstream effectorsOsteoblast differentiationCellular responsesPI3Attachment structuresEffector actionOsteoclast survivalRegulationRecent evidenceImportant roleTransductionRole
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
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidence