2002
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5. New England Journal Of Medicine 2002, 346: 1513-1521. PMID: 12015390, DOI: 10.1056/nejmoa013444.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBone DensityCase-Control StudiesChromosomes, Human, Pair 11FemaleGenes, DominantGenotypeHumansIntercellular Signaling Peptides and ProteinsLDL-Receptor Related ProteinsLow Density Lipoprotein Receptor-Related Protein-5MaleMandibleMutation, MissenseOsteogenesisPalatePedigreePoint MutationProteinsProto-Oncogene ProteinsRadiographyReceptors, LDLSignal TransductionSyndromeWnt ProteinsZebrafish ProteinsConceptsLow-density lipoprotein receptor-related protein 5Higher bone densityProtein 5Bone densityDevelopmental proteinsLipoprotein receptor-related protein 5Fruit flyGenetic analysisDeep mandibleWnt activityTorus palatinusWnt pathwayFunction mutationsWntMajor public health problemNormal glycineBiochemical analysisMutationsTreatment of osteoporosisHigh bone massPublic health problemCodon 171Potential targetAutosomal dominant syndromeGenes
2000
Parathyroid 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
1994
Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing.
Yang KH, dePapp AE, Soifer NE, Dreyer BE, Wu TL, Porter SE, Bellantoni M, Burtis WJ, Insogna KL, Broadus AE. Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing. Biochemistry 1994, 33: 7460-9. PMID: 8003511, DOI: 10.1021/bi00189a054.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsChromatography, AffinityChromatography, High Pressure LiquidCricetinaeCricetulusCulture Media, ConditionedHumansImmunohistochemistryMolecular Sequence DataParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsProtein Processing, Post-TranslationalProteinsTumor Cells, CulturedConceptsHormone-related proteinCarboxy-terminal fragmentCell linesTissue-specific posttranslational processingRat insulinoma cellsDistinct paracrineHuman PTHrP geneHumoral hypercalcemiaMalignant tumorsAutocrine roleRIN cell linesMidregion fragmentPTHrP isoformsMost human cell linesNonmalignant tissuesPhysiological rationalePTHrP geneInsulinoma cellsChinese hamster ovary cellsHuman cell linesHamster ovary cellsSecretory formCellsOvary cellsPosttranslational processing
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 releasePTHHuman granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro.
Gutmann JN, Burtis WJ, Dreyer BE, Andrade-Gordon P, Penzias AS, Polan ML, Insogna KL. Human granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro. The Journal Of Clinical Endocrinology & Metabolism 1993, 76: 1314-1318. PMID: 8496323, DOI: 10.1210/jcem.76.5.8496323.Peer-Reviewed Original ResearchConceptsGranulosa-luteal cellsOvarian follicular fluidImmunoradiometric assayHuman granulosa-luteal cellsHuman ovarian follicular fluidCultured granulosa-luteal cellsParathyroid hormone-related proteinSubsequent prospective analysisAdenylate cyclase-stimulating activityHormone-related proteinCyclase-stimulating activityPresence of mRNAPossible paracrineShort-term culturePTHrP levelsNormal mammalian tissuesBasal secretionImmunohistochemical studyFollicular fluidAutocrine rolePTHrP immunoreactivityProspective analysisPTHrPPTHImmunoreactivity
1992
Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types.
Soifer NE, Dee KE, Insogna KL, Burtis WJ, Matovcik LM, Wu TL, Milstone LM, Broadus AE, Philbrick WM, Stewart AF. Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types. Journal Of Biological Chemistry 1992, 267: 18236-18243. PMID: 1517251, DOI: 10.1016/s0021-9258(19)37178-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCarcinoma, Renal CellCell LineElectrophoresis, Polyacrylamide GelFluorescent Antibody TechniqueHumansImmunohistochemistryKidney NeoplasmsKineticsMolecular Sequence DataParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsProtein BiosynthesisProteinsTransfectionConceptsMid-region fragmentCell typesSecretory formBasic amino acid motifHormone-related proteinAmino acid motifsImportant biological functionsAmino acid sequenceExtensive post-translational processingPost-translational processingDifferent cell typesHuman renal carcinoma cellsInterspecies conservationSodium dodecyl sulfate-polyacrylamide gel electrophoresis analysisRenal carcinoma cellsAcid motifGel electrophoresis analysisAcid sequenceBiological functionsParathyroid hormone-related proteinRegion-specific immunoassaysRat insulinoma cellsCell extractsCleavage siteAmino acidsParathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length
Mitnick M, Isales C, Paliwal I, Insogna K. Parathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length. Journal Of Bone And Mineral Research 1992, 7: 887-896. PMID: 1332431, DOI: 10.1002/jbmr.5650070805.Peer-Reviewed Original ResearchConceptsCyclic AMP accumulationPGE2 releaseAMP accumulationCultured fetal rat long bonesFetal rat long bonesSaos-2 cellsBone resorptive actionProstaglandin E2 secretionBone-active cytokineHormone-related proteinPrimary human bone cell culturesRelease of PGE2Prostaglandin E2 releaseEffects of PTHrPRat long bonesForm of PTHrPHuman osteoblast-like cellsMalignancy syndromeE2 secretionHumoral hypercalcemiaBasal secretionPGE2 secretionE2 releaseOsteoblast-like cellsPTHrPSynthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo
Weir E, Terwilliger G, Sartori L, Insogna K. Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo. Calcified Tissue International 1992, 51: 30-34. PMID: 1393774, DOI: 10.1007/bf00296214.Peer-Reviewed Original ResearchConceptsBovine parathyroid hormoneSerum calciumParathyroid hormone-like proteinDaily subcutaneous injectionsPotent bone-resorbing agentHormone-related proteinDose-dependent increaseDry bone weightHighest dose levelHormone-like proteinBone-resorbing agentsBone dry weightLow dosage levelsHumoral hypercalcemiaParathyroid hormoneDihydroxyvitamin DMale SpragueDawley ratsSubcutaneous injectionHuman PTHrPBone calciumAnabolic agentsPTHrP actionDose levelsHigh doses
1991
Immunoaffinity purification of parathyroid hormone‐related protein from bovine milk and human keratinocyte‐conditioned medium
Stewart A, Wu T, Insogna K, Milstone L, Burtis W. Immunoaffinity purification of parathyroid hormone‐related protein from bovine milk and human keratinocyte‐conditioned medium. Journal Of Bone And Mineral Research 1991, 6: 305-311. PMID: 2035357, DOI: 10.1002/jbmr.5650060313.Peer-Reviewed Original Research
1990
Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase
Brown G, Morris C, Mitnick M, Insogna K. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Journal Of Bone And Mineral Research 1990, 5: 1037-1041. PMID: 1964358, DOI: 10.1002/jbmr.5650051007.Peer-Reviewed Original ResearchConceptsSerum calciumBone resorptionHumoral hypercalcemiaCarbonic anhydrase inhibitorsNephrogenous cyclic AMP excretionCyclic AMP excretionMean serum calciumOsteoclastic bone resorptionDrug-treated animalsLeydig cell tumorMechanism of actionUrine phosphorusUrine calciumSerum phosphorusCell tumorsAcetazolamide treatmentHypercalcemiaSignificant fallFisher ratsObserved hypercalcemiaResorptionDirect inhibitionSignificant riseMalignancyRatsTHE PARATHYROID HORMONE-RELATED PROTEIN STIMULATES HUMAN OSTEOBLAST-LIKE CELLS TO SECRETE A 9,000 DALTON BONERESORBING PROTEIN
Morris CA, Mitnick ME, Weir EC, Horowitz M, Kreider BL, Insogna KL. THE PARATHYROID HORMONE-RELATED PROTEIN STIMULATES HUMAN OSTEOBLAST-LIKE CELLS TO SECRETE A 9,000 DALTON BONERESORBING PROTEIN. Endocrinology 1990, 126: 1783-1786. PMID: 2307127, DOI: 10.1210/endo-126-3-1783.Peer-Reviewed Original ResearchConceptsParathyroid hormone-related proteinBone-resorbing activityHormone-related proteinBone resorptionPTH/Bone-resorbing cytokinesIL-1GM-CSFSingle fractionSequential reverse-phase HPLCII cellsUntreated cellsKD fractionHuman osteoblast-like cellsResorptionSize-exclusion HPLCNgeqOsteoblast-like cellsSpecific activityCellsKD proteinOsteoblastsReversed-phase HPLCCytokinesPGE2
1989
Synthetic Parathyroid Hormone-Like Protein-(1–74): Biochemical and Physiological Characterization*
STEWART A, ELLIOT J, BURTIS W, WU T, INSOGNA K. Synthetic Parathyroid Hormone-Like Protein-(1–74): Biochemical and Physiological Characterization*. Endocrinology 1989, 124: 642-648. PMID: 2912692, DOI: 10.1210/endo-124-2-642.Peer-Reviewed Original ResearchConceptsAmino acid compositionDirect amino acid sequencingAmino acid sequencingAcid compositionPhysiological characterizationN-terminusParathyroid hormone-like proteinRenal cortical adenylate cyclaseFetal rat long bonesInternal sequencesTransduction mechanismsCortical adenylate cyclasePhysiological comparisonPTH-like proteinHormone-like proteinProteolytic fragmentsRat long bonesAdenylate cyclase assayBovine PTHProteinPTH receptorFull-length peptidePeptide hormonesSynthetic peptidesNovel class
1987
Skin-Derived Fibroblasts Respond to Human Parathyroid Hormone-Like Adenylate Cyclase-Stimulating Proteins*
WU T, INSOGNA K, HOUGH L, MILSTONE L, STEWART A. Skin-Derived Fibroblasts Respond to Human Parathyroid Hormone-Like Adenylate Cyclase-Stimulating Proteins*. The Journal Of Clinical Endocrinology & Metabolism 1987, 65: 105-109. PMID: 3034948, DOI: 10.1210/jcem-65-1-105.Peer-Reviewed Original ResearchConceptsPTH-like factorHumoral hypercalcemiaPTH analogsPTH-responsive adenylate cyclaseDermal fibroblast linesAdenylate cyclaseTumor-derived factorsAdenylate cyclase responseDermal fibroblastsAdenylate cyclase stimulationHuman dermal fibroblastsM bovine PTHDermal physiologyFibroblast linesHuman dermal fibroblast linesBovine PTHHigh prevalenceTumor extractsCyclase responseSkin-derived fibroblastsCyclase stimulationPTHKeratinocyte-conditioned mediumHuman tumorsApparent potency