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
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
The liver throws the skeleton a bone (resorption factor)
Chung C, Insogna KL. The liver throws the skeleton a bone (resorption factor). Hepatology 2016, 64: 977-979. PMID: 27312397, PMCID: PMC4992574, DOI: 10.1002/hep.28688.Peer-Reviewed Original ResearchLongitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV
Hsieh E, Fraenkel L, Han Y, Xia W, Insogna KL, Yin MT, Zhu T, Cheng X, Li T. Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV. AIDS 2016, 30: 1935-1942. PMID: 27124896, PMCID: PMC4949136, DOI: 10.1097/qad.0000000000001131.Peer-Reviewed Original ResearchConceptsTenofovir disoproxil fumarateVitamin DProcollagen type 1 N-terminal propeptideInitiation of TDFTenofovir/lamivudine/efavirenzVitamin D binding protein (VDBP) levelsCollagen type 1 cross-linked C-telopeptideIntact parathyroid hormone levelsCross-linked C-telopeptideIntact parathyroid hormoneParathyroid hormone levelsTotal procollagen type 1 N-terminal propeptideBinding protein levelsProtein levelsMulticenter clinical trialPlasma samplesOngoing multicenter clinical trialsN-terminal propeptideClinical characteristicsParathyroid hormoneBone lossFormation markersDisoproxil fumarateC-telopeptideBone resorption
2014
Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV
Hsieh E, Fraenkel L, Xia W, Hu YY, Han Y, Insogna K, Yin MT, Xie J, Zhu T, Li T. Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV. Osteoporosis International 2014, 26: 1035-1044. PMID: 25224293, PMCID: PMC4334679, DOI: 10.1007/s00198-014-2874-3.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusLopinavir/ritonavirBone turnover markersBone resorption marker levelsResorption marker levelsNon-Chinese populationsAntiretroviral therapyTreatment failureImmunodeficiency virusMarker levelsSkeletal metabolismC-terminal cross-linking telopeptideLopinavir/ritonavir therapyTreatment-naïve patientsFirst-line therapyBone resorption markersProcollagen type 1Multi-center trialPlasma samplesChinese individualsN-terminal propeptideType 1 collagenRitonavir therapyTurnover markersResorption markersDenosumab for Treatment of Hypercalcemia of Malignancy
Hu MI, Glezerman IG, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Ying W, Braun A, Jain RK. Denosumab for Treatment of Hypercalcemia of Malignancy. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: 3144-3152. PMID: 24915117, PMCID: PMC4154084, DOI: 10.1210/jc.2014-1001.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyProportion of patientsDay 10Serum calciumBone resorptionCommon serious adverse eventsMedian response durationSerious adverse eventsSerum calcium levelsTreatment of hypercalcemiaDuration of responseNew treatment optionsBisphosphonate therapyPrimary endpointSecondary endpointsAdverse eventsBisphosphonate treatmentDurable responsesComplete responseAdvanced cancerTreatment optionsHematologic malignanciesResponse durationDenosumabCalcium levels
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
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
An Aerobic Weight-Loaded Pilot Exercise Intervention for Breast Cancer Survivors: Bone Remodeling and Body Composition Outcomes
Knobf MT, Insogna K, DiPietro L, Fennie K, Thompson AS. An Aerobic Weight-Loaded Pilot Exercise Intervention for Breast Cancer Survivors: Bone Remodeling and Body Composition Outcomes. Biological Research For Nursing 2008, 10: 34-43. PMID: 18705153, PMCID: PMC3540790, DOI: 10.1177/1099800408320579.Peer-Reviewed Original ResearchMeSH KeywordsAbsorptiometry, PhotonAnalysis of VarianceBody CompositionBody WeightBone ResorptionBreast NeoplasmsClinical Nursing ResearchCollagen Type IExerciseExercise TherapyFeasibility StudiesFemaleHumansMiddle AgedObesityOsteocalcinPerimenopausePilot ProjectsSurvivorsTime FactorsTreatment OutcomeWeight LiftingConceptsBreast cancer survivorsExercise interventionCancer survivorsBone remodelingBone lossFat massBody compositionTreadmill 3 times/weekDual-energy absorptiometry scansWeight gainNovel exercise interventionPilot exercise interventionYears of menopauseAdjuvant endocrine therapyBody composition outcomesOne-group pre-posttest designTimes/weekSerum NTxEndocrine therapySerum osteocalcinMean ageSerum biomarkersBone massHigh adherenceHigh riskProton pump-inhibiting drugs, calcium homeostasis, and bone health
Wright MJ, Proctor DD, Insogna KL, Kerstetter JE. Proton pump-inhibiting drugs, calcium homeostasis, and bone health. Nutrition Reviews 2008, 66: 103-108. PMID: 18254877, DOI: 10.1111/j.1753-4887.2008.00015.x.BooksMeSH KeywordsBone and BonesBone DensityBone ResorptionCalciumFractures, BoneHip FracturesHumansProton Pump Inhibitors
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 Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women
Kerstetter JE, O’Brien K, Caseria DM, Wall DE, Insogna KL. The Impact of Dietary Protein on Calcium Absorption and Kinetic Measures of Bone Turnover in Women. The Journal Of Clinical Endocrinology & Metabolism 2004, 90: 26-31. PMID: 15546911, DOI: 10.1210/jc.2004-0179.Peer-Reviewed Original ResearchMeSH KeywordsAdultBone ResorptionCalciumDietary ProteinsFemaleHumansIntestinal AbsorptionKineticsOsteogenesisConceptsHigh-protein dietUrinary calciumBone turnoverCalcium absorptionDual-stable calcium isotopesAdditional urinary calciumIntestinal calcium absorptionHealthy womenStable calcium isotopesBone balanceNonsignificant trendSkeletal resorptionCalcium kineticsAcid loadBone originProtein-induced effectsLevels of proteinRandom orderDietary proteinDietHypercalciuriaWomenExperimental dietsSignificant reductionCalcium
2003
Low Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans
Kerstetter JE, O'Brien KO, Insogna KL. Low Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans. Journal Of Nutrition 2003, 133: 855s-861s. PMID: 12612169, DOI: 10.1093/jn/133.3.855s.BooksConceptsIntestinal calcium absorptionLow-protein dietCalcium absorptionHigh-protein dietProtein dietSecondary hyperparathyroidismUrinary calciumBone resorptionDietary proteinAdditional urinary calciumDietary protein resultsSerum parathyroid hormoneNutrition intervention trialCalcium balance studiesRecent epidemiological studiesLow protein intakeNutrition intervention studiesParathyroid hormoneBone lossSkeletal healthIntervention trialsCalcium metabolismSkeletal fracturesBone densityLong-term consequences
2002
Circulating Levels of Interleukin-6 Soluble Receptor Predict Rates of Bone Loss in Patients with Primary Hyperparathyroidism
Nakchbandi IA, Mitnick MA, Lang R, Gundberg C, Kinder B, Insogna K. Circulating Levels of Interleukin-6 Soluble Receptor Predict Rates of Bone Loss in Patients with Primary Hyperparathyroidism. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 4946-4951. PMID: 12414855, DOI: 10.1210/jc.2001-011814.Peer-Reviewed Original ResearchConceptsBone lossIL-6sRTotal femurIL-6IL-6 soluble receptorPrimary hyperparathyroidism resultsYearly bone lossSubset of patientsUntreated hyperparathyroidismDisease activityPrimary hyperparathyroidismUpper tertileCytokine axisHyperparathyroidismSoluble receptorPatientsBiochemical markersClassical biochemical markersWhole groupFemurPredict rateGreater rateRecent studiesTertileGroupRole of the interleukin-6/interleukin-6 soluble receptor cytokine system in mediating increased skeletal sensitivity to parathyroid hormone in perimenopausal women.
Insogna K, Mitnick M, Pascarella J, Nakchbandi I, Grey A, Masiukiewicz U. Role of the interleukin-6/interleukin-6 soluble receptor cytokine system in mediating increased skeletal sensitivity to parathyroid hormone in perimenopausal women. Journal Of Bone And Mineral Research 2002, 17 Suppl 2: n108-16. PMID: 12412787.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBone and BonesBone ResorptionCollagenCollagen Type ICytokinesDisease Models, AnimalEstrogensFemaleFollow-Up StudiesHumansHyperparathyroidismInterleukin-6MenopauseMiceMiddle AgedOsteoporosis, PostmenopausalParathyroid HormonePeptidesPostmenopausePredictive Value of TestsPremenopauseReceptors, Interleukin-6Reference ValuesRetrospective StudiesConceptsIL-6/ILInterleukin-6Skeletal sensitivityPerimenopausal periodPrimary hyperparathyroidismPerimenopausal womenCytokine systemInterleukin-6 soluble receptorSerum IL-6 valuesEstrogen-deficient stateUrine N-telopeptideInterleukin-6/interleukinAction of PTHGroup of patientsIL-6 valuesSerum IL-6/ILEstrogen modulatesIL-6sRIL-6sR.Perimenopausal groupUrine NTXPremenopausal womenSkeletal complicationsCytokine profileExaggerated releaseEvidence that the IL-6/IL-6 Soluble Receptor Cytokine System Plays a Role in the Increased Skeletal Sensitivity to PTH in Estrogen-Deficient Women
Masiukiewicz US, Mitnick M, Gulanski BI, Insogna KL. Evidence that the IL-6/IL-6 Soluble Receptor Cytokine System Plays a Role in the Increased Skeletal Sensitivity to PTH in Estrogen-Deficient Women. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 2892-2898. PMID: 12050269, DOI: 10.1210/jcem.87.6.8577.Peer-Reviewed Original ResearchConceptsEstrogen-deficient womenIL-6/ILSkeletal sensitivityIL-6IL-6sREstrogen deficiencyCytokine systemIL-6 soluble receptorUrine N-telopeptideAction of PTHPrevious animal studiesNTx excretionPTH infusionPostmenopausal womenSerum calciumN-telopeptideCytokine productionTNF-alphaExaggerated increaseIL-1betaHormonal statusBaseline valuesSoluble receptorAnimal studiesColony-stimulating factor-1
2000
POSTTRANSPLANT BONE DISEASE: EVIDENCE FOR A HIGH BONE RESORPTION STATE
Cayco A, Wysolmerski J, Simpson C, Mitnick M, Gundberg C, Kliger A, Lorber M, Silver D, Basadonna G, Friedman A, Insogna K, Cruz D, Bia M. POSTTRANSPLANT BONE DISEASE: EVIDENCE FOR A HIGH BONE RESORPTION STATE. Transplantation 2000, 70: 1722-1728. PMID: 11152104, DOI: 10.1097/00007890-200012270-00011.Peer-Reviewed Original ResearchConceptsLong-term renal transplant recipientsRenal transplant recipientsBone mineral densityTransplant recipientsBone lossBone resorptionFirst post-transplant yearCumulative prednisone doseElevated urinary levelsIntact parathyroid hormonePercent of patientsDuration of dialysisPost-transplant yearPrevalence of osteoporosisCross-sectional studyLoss of boneBone resorption statePrednisone doseYear posttransplantIntact PTHRenal transplantLevels of calciumRenal functionSerum levelsTransplant yearEstrogen 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
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