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
Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia
Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia. The Journal Of Clinical Pharmacology 2015, 56: 176-185. PMID: 26073451, PMCID: PMC5042055, DOI: 10.1002/jcph.570.Peer-Reviewed Original ResearchConceptsConcentration-time curveSerum fibroblast growth factor 23Multiple ascending dose trialFibroblast growth factor 23Ascending dose trialHuman IgG1 monoclonal antibodyLow-normal serumRecombinant human IgG1 monoclonal antibodyDihydroxyvitamin D concentrationsGlomerular filtration rateGrowth factor 23Serum inorganic phosphorusSerum Pi concentrationIgG1 monoclonal antibodyFGF23 antibodyDose adjustmentFactor 23Serum PiFiltration ratePhosphate reabsorptionBone markersKRN23D concentrationsNormal serumMonoclonal antibodiesThe Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults
Kerstetter JE, Bihuniak JD, Brindisi J, Sullivan RR, Mangano KM, Larocque S, Kotler BM, Simpson CA, Cusano A, Gaffney-Stomberg E, Kleppinger A, Reynolds J, Dziura J, Kenny AM, Insogna KL. The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 2214-2222. PMID: 25844619, PMCID: PMC4454800, DOI: 10.1210/jc.2014-3792.Peer-Reviewed Original ResearchConceptsBone mineral densityBone resorptionL-spine bone mineral densitySelf-reported protein intakeDual-energy X-ray absorptiometryTruncal lean massPlacebo-controlled trialGlomerular filtration rateBody mass indexProtein supplementationC-terminal telopeptideX-ray absorptiometryFat-free massWhey protein supplementHigh-protein dietHealthy older adultsOlder Caucasian adultsUrine calciumRenal functionMass indexSkeletal healthUsual dietFiltration rateMineral densityBone massThe effects of dietary protein and amino acids on skeletal metabolism
Bihuniak JD, Insogna KL. The effects of dietary protein and amino acids on skeletal metabolism. Molecular And Cellular Endocrinology 2015, 410: 78-86. PMID: 25843057, PMCID: PMC5852680, DOI: 10.1016/j.mce.2015.03.024.BooksConceptsDietary proteinDietary protein intakeOptimal skeletal growthRecent data bearingSkeletal healthCalcium economyMineral metabolismSkeletal metabolismProtein intakeDietary allowanceSkeletal homeostasisNutrient intakeSkeletal massIntakeSkeletal growthSite-specific effectsMolecular mechanismsMetabolismVariable levelsLife continuumProtein
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
2013
Dietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial
Bihuniak JD, Simpson CA, Sullivan RR, Caseria DM, Kerstetter JE, Insogna KL. Dietary Protein-Induced Increases in Urinary Calcium Are Accompanied by Similar Increases in Urinary Nitrogen and Urinary Urea: A Controlled Clinical Trial. Journal Of The Academy Of Nutrition And Dietetics 2013, 113: 447-451. PMID: 23438496, PMCID: PMC5868414, DOI: 10.1016/j.jand.2012.11.002.Peer-Reviewed Original ResearchConceptsBone turnover markersDietary protein intakeUrinary creatinineUrinary calciumProtein intakeUrinary ureaTurnover markersUrinary nitrogenNutrition intervention trialMaltodextrin controlPostmenopausal womenIntervention trialsClinical trialsUrinary metabolitesCreatinineDay 0Whey supplementationWhey supplementsIntakeSample t-testSimilar increaseTrialsT-testSupplementationMarkers
2012
Phosphorus-31 MRI of hard and soft solids using quadratic echo line-narrowing
Frey MA, Michaud M, VanHouten JN, Insogna KL, Madri JA, Barrett SE. Phosphorus-31 MRI of hard and soft solids using quadratic echo line-narrowing. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5190-5195. PMID: 22431609, PMCID: PMC3325667, DOI: 10.1073/pnas.1117293109.Peer-Reviewed Original Research
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 analysisChemokinesDietary protein and skeletal health: a review of recent human research
Kerstetter JE, Kenny AM, Insogna KL. Dietary protein and skeletal health: a review of recent human research. Current Opinion In Lipidology 2011, 22: 16-20. PMID: 21102327, PMCID: PMC4659357, DOI: 10.1097/mol.0b013e3283419441.BooksConceptsSkeletal healthBone healthDietary proteinBone resorptionCalcium retentionInsulin-like growth factor-1Recent human researchOsteoclastic bone resorptionBone mineral densityHigh protein intakeLean body massGrowth factor-1High-protein dietMeta-analysis studyVitamin DDietary calciumCalcium absorptionCalcium metabolismBone metabolismClinical trialsMineral densityBone balanceBone massMetabolic acid loadSystemic pH
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 differencesTargeted 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 osteoblastsThe Effect of Dietary Protein on Intestinal Calcium Absorption in Rats
Gaffney-Stomberg E, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL. The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats. Endocrinology 2010, 151: 1071-1078. PMID: 20147526, PMCID: PMC2840679, DOI: 10.1210/en.2009-0744.Peer-Reviewed Original ResearchConceptsIntestinal Ca absorptionCa absorptionHigh-protein dietUrinary calciumBrush border membrane vesiclesProtein intakeFemale Sprague-Dawley ratsProtein dietProtein intake resultsIntestinal calcium absorptionDietary protein intakeHigh protein intakeSprague-Dawley ratsLow-protein groupHigh protein groupDietary protein effectsCalcium absorptionAcute increaseDawley ratsDuodenal mucosaIntake resultsRatsCa balanceTranscellular CaDietary protein
2009
The Effect of Proton Pump-Inhibiting Drugs on Mineral Metabolism
Insogna KL. The Effect of Proton Pump-Inhibiting Drugs on Mineral Metabolism. The American Journal Of Gastroenterology 2009, 104: ajg200944. PMID: 19262542, DOI: 10.1038/ajg.2009.44.BooksConceptsProton pump inhibitorsMineral metabolismLong-term proton pump inhibitorsIntestinal calcium absorptionHip fracture ratesClass of drugsFragility fracturesBone lossCalcium economyPump inhibitorsCalcium absorptionFracture ratesCalcium balanceSkeletal homeostasisGreater riskAdverse effectsHigh rateDrugsRecent studiesMetabolismLong termWhere Wnts Went: The Exploding Field of Lrp5 and Lrp6 Signaling in Bone*
Williams BO, Insogna KL. Where Wnts Went: The Exploding Field of Lrp5 and Lrp6 Signaling in Bone*. Journal Of Bone And Mineral Research 2009, 24: 171-178. PMID: 19072724, PMCID: PMC3276354, DOI: 10.1359/jbmr.081235.BooksConceptsEffects of WntWnt pathwayBone metabolismDuodenal enterochromaffin cellsBone anabolic agentAction of WntNoncanonical signaling pathwaysRegulation of sclerostinDownstream effector moleculesEndogenous Wnt inhibitorsBone cell metabolismImportant regulatory moleculesAnabolic actionEnterochromaffin cellsSmall molecule inhibitorsSerotonin synthesisDrug discoveryTrophic stimuliNew therapiesBone anabolismAnabolic agentsTherapeutic targetEndocrine fashionFinal pathwayCentral regulator
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 absenceProton 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
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
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
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