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
2015
Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo
Zhu M, Sun B, Saar K, Simpson C, Troiano N, Dallas SL, Tiede‐Lewis L, Nevius E, Pereira JP, Weinstein RS, Tommasini SM, Insogna KL. Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age‐Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. Journal Of Bone And Mineral Research 2015, 31: 864-873. PMID: 26496249, PMCID: PMC4826801, DOI: 10.1002/jbmr.2733.Peer-Reviewed Original ResearchConceptsDual-energy X-ray absorptiometryBone mineral densityDKO miceParathyroid hormoneOsteoclast numberDKO animalsSerum cross-linked C-telopeptideCross-linked C-telopeptideDaily parathyroid hormoneTrabecular bone massX-ray absorptiometryMetaphyseal trabecular boneNormal differentiation markersAge-dependent changesC-telopeptideMineral densityBone massBone densityActin ring formationSkeletal metabolismOsteoblast numberTooth eruptionResorptive activityNormal responseFocal disruption
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-RegulationControl of bone formation by the serpentine receptor Frizzled-9
Albers J, Schulze J, Beil FT, Gebauer M, Baranowsky A, Keller J, Marshall RP, Wintges K, Friedrich FW, Priemel M, Schilling AF, Rueger JM, Cornils K, Fehse B, Streichert T, Sauter G, Jakob F, Insogna KL, Pober B, Knobeloch KP, Francke U, Amling M, Schinke T. Control of bone formation by the serpentine receptor Frizzled-9. Journal Of Cell Biology 2011, 192: 1057-1072. PMID: 21402791, PMCID: PMC3063134, DOI: 10.1083/jcb.201008012.Peer-Reviewed Original ResearchConceptsBone formationLow bone massBone loss disordersPotential downstream mediatorsBone massUbiquitin-like modifier ISG15Interferon-regulated genesTherapeutic implicationsLoss disordersCanonical Wnt signalingBone remodelingFrizzled 9Reduced expressionDownstream mediatorDifferentiation markersWnt signalingWnt receptorsNormal expressionPrimary osteoblastsFZD9OsteoblastsOsteoblast differentiationMatrix mineralizationMolecular analysisChemokines
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
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 absence
2005
Multiple 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
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 ResearchConceptsBody 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 counterpartsThe 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
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
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 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 ResearchConceptsCSF-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-kappaBEstrogen Modulates Parathyroid Hormone-Induced Interleukin-6 Production in Vivo and in Vitro*
Masiukiewicz U, Mitnick M, Grey A, Insogna K. Estrogen Modulates Parathyroid Hormone-Induced Interleukin-6 Production in Vivo and in Vitro*. Endocrinology 2000, 141: 2526-2531. PMID: 10875254, DOI: 10.1210/endo.141.7.7537.Peer-Reviewed Original Research
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
Role 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