2021
An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone
Walker JM, Yao GQ, Siu E, Zhu M, Sun BH, Simpson C, Insogna KL. An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone. Endocrinology 2021, 162: bqab042. PMID: 33640975, PMCID: PMC8095390, DOI: 10.1210/endocr/bqab042.Peer-Reviewed Original ResearchConceptsSphk2-/- miceParathyroid hormoneAnabolic responseFemoral trabecular BV/TVLower spinal bone mineral densityTrabecular BV/TVSpinal bone mineral densityDaily parathyroid hormoneFemoral bone volumeSuppression of sclerostinEnd of treatmentNormal bone massBone mineral densityNormal bone remodelingRole of SphK1BV/TVFemale control animalsSphingosine kinase 2Sphingosine kinaseControl miceLow BMDAnabolic effectsBone massMineral densityControl animalsSelective 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
2018
The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function
Koduru SV, Sun BH, Walker JM, Zhu M, Simpson C, Dhodapkar M, Insogna KL. The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function. Journal Of Biological Chemistry 2018, 293: 15055-15069. PMID: 30082316, PMCID: PMC6166722, DOI: 10.1074/jbc.ra117.000633.Peer-Reviewed Original ResearchConceptsOsteoclast formationTSP-1Competitive NO synthase inhibitorPro-osteoclastogenic effectAntibody-mediated blockadeNitroarginine methyl esterNO synthase inhibitorNitric Oxide SignalingPTH infusionDifferentiation 47Parathyroid hormoneBone resorptionFemale miceHypercalcemic responseOsteoclast maturationSynthase inhibitorResorptive activitySynthetic agonistsCD36Osteoclast progenitorsMiceInhibitory effectCD47OsteoclastsWT osteoblasts
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
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 disruptionAgRP Neurons Regulate Bone Mass
Kim JG, Sun BH, Dietrich MO, Koch M, Yao GQ, Diano S, Insogna K, Horvath TL. AgRP Neurons Regulate Bone Mass. Cell Reports 2015, 13: 8-14. PMID: 26411686, PMCID: PMC5868421, DOI: 10.1016/j.celrep.2015.08.070.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusBone DensityBone Diseases, MetabolicFemurGene Expression RegulationHomeostasisHypothalamusIon ChannelsLeptinMaleMiceMice, KnockoutMitochondrial ProteinsNeuronsNorepinephrinePhenotypePropranololReceptors, Adrenergic, betaReceptors, LeptinSignal TransductionSirtuin 1TibiaUncoupling Protein 2ConceptsAgRP neuronsCell-autonomous deletionSignificant regulatory roleAgRP neuronal functionBone massLeptin receptor deletionSkeletal bone metabolismTransgenic animalsRegulatory roleGene deletionBone homeostasisDeletionNeuronal functionPostnatal deletionSympathetic toneReceptor deletionArcuate nucleusLeptin actionBone metabolismSkeletal metabolismMultiple linesNeuronsMiceMetabolismCircuit integrity
2014
The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*
Yao C, Yao GQ, Sun BH, Zhang C, Tommasini SM, Insogna K. The Transcription Factor T-box 3 Regulates Colony-stimulating Factor 1-dependent Jun Dimerization Protein 2 Expression and Plays an Important Role in Osteoclastogenesis*. Journal Of Biological Chemistry 2014, 289: 6775-6790. PMID: 24394418, PMCID: PMC3945339, DOI: 10.1074/jbc.m113.499210.Peer-Reviewed Original Research
2012
LIM kinase 1 deficient mice have reduced bone mass
Kawano T, Zhu M, Troiano N, Horowitz M, Bian J, Gundberg C, Kolodziejczak K, Insogna K. LIM kinase 1 deficient mice have reduced bone mass. Bone 2012, 52: 70-82. PMID: 23017662, PMCID: PMC3688839, DOI: 10.1016/j.bone.2012.09.024.Peer-Reviewed Original ResearchConceptsLIM kinase 1Cytoskeletal remodelingRole of LIMK1Specialized cellular functionsActin cytoskeletal remodelingActin-severing proteinBone cell biologyNormal osteoblast differentiationCellular functionsCell biologyCell motilityCell shapeKinase 1Cell cycleF-actinOsteoblast differentiationPhospho-cofilinActin monomersSkeletal phenotypeOsteoblast coloniesOsteoblastsMetalloproteinase activityDifferentiationRemodelingRate of mineralization
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
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
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
Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover
Xie D, Cheng H, Hamrick M, Zhong Q, Ding KH, Correa D, Williams S, Mulloy A, Bollag W, Bollag RJ, Runner RR, McPherson JC, Insogna K, Isales CM. Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover. Bone 2005, 37: 759-769. PMID: 16219496, DOI: 10.1016/j.bone.2005.06.021.Peer-Reviewed Original ResearchConceptsGlucose-dependent insulinotropic polypeptideGipr-/- miceReceptor knockout miceBone turnoverBone massGlucose-dependent insulinotropic polypeptide receptor knockout miceKnockout miceRole of GIPGIP receptor knockout miceEffects of GIPLow bone massBiomechanical bone strengthWild-type miceLean body massEarly age-related changesAge-related changesIncretin hormonesSerum markersMeal ingestionInsulinotropic polypeptideAnabolic effectsBone densityBone microarchitectureNutrient ingestionVivo effects
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
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-kappaBParathyroid 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
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