2021
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
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
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
2001
Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor
Mitnick M, Grey A, Masiukiewicz U, Bartkiewicz M, Rios-Velez L, Friedman S, Xu L, Horowitz M, Insogna K. Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor. AJP Endocrinology And Metabolism 2001, 280: e405-e412. PMID: 11171594, DOI: 10.1152/ajpendo.2001.280.3.e405.Peer-Reviewed Original ResearchConceptsInterleukin-6IL-6sRParathyroid hormoneSoluble receptorBioactive interleukin-6Hepatic IL-6 productionBioactive IL-6IL-6 productionType 1 receptorHepatic stellate cellsDose-dependent productionIsolated rat liverHepatic endothelial cellsIL-6sR.Serum levelsBone resorptionHepatic productionEndocrine effectsKupffer cellsStellate cellsPTHImportant mediatorEndothelial cellsLiverHormone
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
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
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 riseMalignancyRats
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 classSynthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*
THORIKAY M, KRAMER S, REYNOLDS F, SORVILLO J, DOESCHER L, WU T, MORRIS C, BURTIS W, INSOGNA K, VALENZUELA D, STEWART A. Synthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*. Endocrinology 1989, 124: 111-118. PMID: 2535801, DOI: 10.1210/endo-124-1-111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBiological AssayBone and BonesCalciumCloning, MolecularCyclic AMPDNADogsEscherichia coliGenes, SyntheticKidneyMolecular Sequence DataMolecular WeightNeoplasm ProteinsOsteosarcomaParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsPlasmidsRatsRecombinant ProteinsTumor Cells, Cultured
1986
Two Species of Adenylate Cyclase-Stimulating Activity in a Murine Squamous Carcinoma Model of Humoral Hypercalcemia of Malignancy*
BURTIS W, BROADUS A, INSOGNA K, WEIR E, STEWART A. Two Species of Adenylate Cyclase-Stimulating Activity in a Murine Squamous Carcinoma Model of Humoral Hypercalcemia of Malignancy*. Endocrinology 1986, 118: 1982-1988. PMID: 3009144, DOI: 10.1210/endo-118-5-1982.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBiological AssayCarcinoma, Squamous CellChromatography, High Pressure LiquidDisease Models, AnimalDogsHypercalcemiaKidney CortexMiceNeoplasm ProteinsOsteosarcomaParathyroid HormonePeptide FragmentsRatsReceptors, Cell SurfaceReceptors, Parathyroid HormoneSkin NeoplasmsConceptsAdenylate cyclase-stimulating activityCyclase-stimulating activityTumor extractsPTH antagonistHumoral hypercalcemiaRat osteosarcomaCarcinoma modelDose-response curve parallelRat Leydig cellsAdenylate cyclase activityAdenylate cyclase systemDose-response curvePostreceptor stepPTH (3-34) amideLeydig cellsReversed-phase HPLCCyclase systemCyclase activityPeak IICommon mediatorPTHCyclase assaysHypercalcemiaMalignancyPhase HPLCA Parathyroid Hormone-Like Protein from Cultured Human Keratinocytes
Merendino JJ, Insogna KL, Milstone LM, Broadus AE, Stewart AF. A Parathyroid Hormone-Like Protein from Cultured Human Keratinocytes. Science 1986, 231: 388-390. PMID: 2417317, DOI: 10.1126/science.2417317.Peer-Reviewed Original ResearchConceptsHumoral hypercalcemiaParathyroid hormoneHuman keratinocytesParathyroid hormone receptor agonistsParathyroid hormone-like proteinSquamous epithelial originExtracts of tumorsHormone receptor agonistsHormone-like proteinHormone-like factorsAdenylate cyclase activityRat osteosarcoma cellsAdenylate cyclase productionNative parathyroid hormoneCultured human keratinocytesNormal human keratinocytesReceptor agonistMalignant tumorsCyclic adenosine monophosphateHypercalcemiaEpithelial originKeratinocyte-conditioned mediumMalignancyCyclase activityCyclase production
1983
Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy.
Stewart AF, Insogna KL, Goltzman D, Broadus AE. Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy. Proceedings Of The National Academy Of Sciences Of The United States Of America 1983, 80: 1454-1458. PMID: 6298791, PMCID: PMC393616, DOI: 10.1073/pnas.80.5.1454.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityCyclase-stimulating activityExtracts of tumorsHumoral hypercalcemiaPTH receptorTumor extractsPTH-sensitive adenylate cyclaseAdenylate cyclaseSensitive cytochemical bioassayRenal PTH receptorsParathyroid hormoneClinical studiesPTH resultsCompetitive inhibition studiesCytochemical bioassayTumorsPatientsHypercalcemiaGlucose-6-phosphate dehydrogenaseHHMFurther studiesMalignancyPTHFragment analogSpecific binding