2023
Multifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein‐1 (LMP‐1)
Sangadala S, Shore E, Xu M, Bergwitz C, Lozano‐Calderon S, Lin A, Boden S, Kaplan F. Multifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein‐1 (LMP‐1). American Journal Of Medical Genetics Part A 2023, 191: 2164-2174. PMID: 37218523, DOI: 10.1002/ajmg.a.63304.Peer-Reviewed Original ResearchConceptsLIM mineralization protein-1Bone morphogenetic protein (BMP) pathwayGermline variantsBone morphogenetic proteinRecombinant BMP-2LMP-1Gene-disease relationshipsC2C12 cellsGenetic analysisIntracellular proteinsWT proteinHeterotopic ossificationProtein pathwayOsteoblast markersWT cellsBMP-2Protein 1Coding variantsGene-diseaseProtein levelsControl cellsPathogenic variantsLMP-1 variantsCo-transfectionMC3T3 cells
2021
Phosphorus bioaccessibility measured in four amino acid–based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice
Chande S, Dijk F, Fetene J, Yannicelli S, Carpenter TO, van Helvoort A, Bergwitz C. Phosphorus bioaccessibility measured in four amino acid–based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice. Nutrition 2021, 89: 111291. PMID: 34111672, PMCID: PMC8588148, DOI: 10.1016/j.nut.2021.111291.Peer-Reviewed Original ResearchConceptsPhosphorus bioavailabilityAmino acid-based formulaProton pump inhibitorsDigestion modelBioavailability analysisPlasma phosphorus levelsLow phosphorus dietDigestion conditionsBioaccessibilityBioavailabilityStomach acidificationDigestive conditionsIntact fibroblast growth factor 23Phosphorus dietFibroblast growth factor 23Stomach pH.Intact parathyroid hormoneAcid-suppressive medicationsDihydroxy vitamin DGrowth factor 23Phosphorus levelsPhosphorus bioaccessibilityAcidificationPhosphorusIntact fibroblast growth factor
2019
Transgenic mouse model for conditional expression of influenza hemagglutinin-tagged human SLC20A1/PIT1
Chande S, Ho B, Fetene J, Bergwitz C. Transgenic mouse model for conditional expression of influenza hemagglutinin-tagged human SLC20A1/PIT1. PLOS ONE 2019, 14: e0223052. PMID: 31613887, PMCID: PMC6793878, DOI: 10.1371/journal.pone.0223052.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBeta-GlobinsBiological TransportBone DensityCalcitriolChickensCytomegalovirusFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsFounder EffectHemagglutinin Glycoproteins, Influenza VirusHumansMaleMiceMice, TransgenicOsteoblastsParathyroid HormonePhosphatesPrimary Cell CulturePromoter Regions, GeneticRabbitsRecombinant Fusion ProteinsSkullTranscription Factor Pit-1TransgenesConceptsPrimary calvaria osteoblastsLoxP-stop-loxPLoxP-STOP-loxP cassetteMouse modelDihydroxy vitamin D levelsHemagglutinin (HABone mineral densityVitamin D levelsInfluenza hemagglutinin (HAConditional mouse modelActivation of transgene expressionElevated plasma PiTransgenic mouse modelPlasma iPTHUrine PiBeta-globin geneSerum calciumWT littermatesMineral densityDays of ageProtein excretionD levelsSemi-quantitative RT-PCRStandard chowTransgenic mice
2018
Role of phosphate sensing in bone and mineral metabolism
Chande S, Bergwitz C. Role of phosphate sensing in bone and mineral metabolism. Nature Reviews Endocrinology 2018, 14: 637-655. PMID: 30218014, PMCID: PMC8607960, DOI: 10.1038/s41574-018-0076-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPi transportersSignal transductionPi homeostasisCellular phosphate homeostasisPhosphate homeostasisExpression of Pi transportersPi-sensing mechanismEssential structural componentIntracellular signal transductionPi transportMulticellular organismsInositol pyrophosphatesIntracellular Pi levelsDomain proteinsRegulation of FGF23 expressionPlasma membranePhosphate sensingDisorders of phosphate homeostasisCell metabolismExtracellular matrixCellular levelHomeostasisTransductionGenetic disordersOrganisms
2017
Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice
Caballero D, Li Y, Fetene J, Ponsetto J, Chen A, Zhu C, Braddock DT, Bergwitz C. Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice. PLOS ONE 2017, 12: e0180098. PMID: 28704395, PMCID: PMC5509111, DOI: 10.1371/journal.pone.0180098.Peer-Reviewed Original ResearchConceptsRenal calcificationCompared to WT miceElevated urinary excretionRenal stone diseaseNucleotide pyrophosphatase phosphodiesterase 1WT miceDietary calciumUrinary excretionIntraperitoneal administrationStone diseaseNull miceMouse mutationMiceCalcificationNephrocalcinosisNpt2aDisordersUnrecognized factorsContribution of genotypePresent studyPhosphodiesterase 1PPINpt2cPatientsNephrolithiasisResponse of Npt2a knockout mice to dietary calcium and phosphorus
Li Y, Caballero D, Ponsetto J, Chen A, Zhu C, Guo J, Demay M, Jüppner H, Bergwitz C. Response of Npt2a knockout mice to dietary calcium and phosphorus. PLOS ONE 2017, 12: e0176232. PMID: 28448530, PMCID: PMC5407772, DOI: 10.1371/journal.pone.0176232.Peer-Reviewed Original ResearchConceptsCompared to WT miceWT miceDietary calciumDietary phosphateCalcium x phosphorus productUrine phosphate levelsUrinary calcium excretionUrine anion gapDevelopment of novel therapiesWild-typeRenal stone diseaseWild-type miceNpt2a-knockout (KO) miceCalcium excretionFGF23 levelsNovel therapiesPreventing nephrolithiasisPlasma phosphateStone diseaseAnion gapAddition of calciumKnockout micePhosphorus productCalcium phosphate depositionHuman carriers
2012
Fanconi-Bickel Syndrome and Autosomal Recessive Proximal Tubulopathy with Hypercalciuria (ARPTH) Are Allelic Variants Caused by GLUT2 Mutations
Mannstadt M, Magen D, Segawa H, Stanley T, Sharma A, Sasaki S, Bergwitz C, Mounien L, Boepple P, Thorens B, Zelikovic I, Jüppner H. Fanconi-Bickel Syndrome and Autosomal Recessive Proximal Tubulopathy with Hypercalciuria (ARPTH) Are Allelic Variants Caused by GLUT2 Mutations. The Journal Of Clinical Endocrinology & Metabolism 2012, 97: e1978-e1986. PMID: 22865906, PMCID: PMC3462928, DOI: 10.1210/jc.2012-1279.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsFamilial Hypophosphatemic RicketsFamily HealthFanconi SyndromeFemaleGenes, RecessiveGenetic VariationGenome-Wide Association StudyGlucose Transporter Type 1Glucose Transporter Type 2HumansHypercalciuriaHypophosphatemia, FamilialKidney Tubules, ProximalMaleMiceMice, TransgenicMolecular Sequence DataOocytesPedigreeRicketsSodium-Phosphate Cotransporter Proteins, Type IIaSodium-Phosphate Cotransporter Proteins, Type IIcXenopus laevisConceptsGlucose transporter 2Sequence analysis of candidate genesCandidate genesSequence analysisGenome-wide linkage scanAnalysis of candidate genesFanconi-Bickel syndromeProximal renal tubulopathyRenal tubulopathyNucleotide sequence analysisGenetic mappingHomozygous mutationPhosphate importLinkage scanMolecular basisXenopus oocytesTransport of glucoseGLUT2 mutationsMolecular levelGenesGlucose transportUrinary phosphate excretionAllelic variantsPhosphate homeostasisDirect nucleotide sequence analysis
2010
Acute Down-regulation of Sodium-dependent Phosphate Transporter NPT2a Involves Predominantly the cAMP/PKA Pathway as Revealed by Signaling-selective Parathyroid Hormone Analogs
Nagai S, Okazaki M, Segawa H, Bergwitz C, Dean T, Potts JT, Mahon MJ, Gardella TJ, Jüppner H. Acute Down-regulation of Sodium-dependent Phosphate Transporter NPT2a Involves Predominantly the cAMP/PKA Pathway as Revealed by Signaling-selective Parathyroid Hormone Analogs. Journal Of Biological Chemistry 2010, 286: 1618-1626. PMID: 21047792, PMCID: PMC3020770, DOI: 10.1074/jbc.m110.198416.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleChlorocebus aethiopsCOS CellsCyclic AMPCyclic AMP-Dependent Protein KinasesDown-RegulationHumansIn Vitro TechniquesKidney Tubules, ProximalMaleMiceMice, Inbred C57BLOpossumsOsteoblastsParathyroid HormonePhosphorusPseudohypoparathyroidismRatsSignal TransductionSodiumSodium-Phosphate Cotransporter Proteins, Type IIaConceptsAcute down-regulationNpt2a expressionParathyroid hormoneRenal proximal tubule cellsParathyroid hormone (PTH)/PTH-related peptideCAMP/PKALong-acting PTH analogPTH analogsWild-type miceRenal proximal tubulesIntracellular calcium responsesParathyroid hormone analogProximal tubule cellsOpossum kidney cellsM-PTH(1Prolonged cAMP responsesParathyroid hormone analoguesCAMP/PKA signaling pathwayPTH-dependent regulationRenal brush border membraneClonal cell linesInducing IP(3Pseudohypoparathyroid patientsMembrane expressionCalcium response
2008
Cellular Mechanism of Decreased Bone in Brtl Mouse Model of OI: Imbalance of Decreased Osteoblast Function and Increased Osteoclasts and Their Precursors*
Uveges TE, Collin‐Osdoby P, Cabral WA, Ledgard F, Goldberg L, Bergwitz C, Forlino A, Osdoby P, Gronowicz GA, Marini JC. Cellular Mechanism of Decreased Bone in Brtl Mouse Model of OI: Imbalance of Decreased Osteoblast Function and Increased Osteoclasts and Their Precursors*. Journal Of Bone And Mineral Research 2008, 23: 1983-1994. PMID: 18684089, PMCID: PMC2686922, DOI: 10.1359/jbmr.080804.Peer-Reviewed Original ResearchConceptsColony-forming unitsRANKL/OPG ratioOsteogenesis imperfectaWildtype valuesCompared to wildtype miceSevere osteogenesis imperfectaReal-time RT-PCRMouse model of OIIncreases osteoclast precursorsBone-resorbing osteoclastsOI therapyKnock-in modelIncreased osteoclastsOsteoclast increaseMarrow culturesWildtype miceModel of OITRACP stainingOsteoblast functionOsteoclast precursorsCellular mechanismsBrtl miceOsteoclastsRT-PCRTRACP(+Genetic Evidence of Serum Phosphate-Independent Functions of FGF-23 on Bone
Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schüler C, Erben RG, Lanske B. Genetic Evidence of Serum Phosphate-Independent Functions of FGF-23 on Bone. PLOS Genetics 2008, 4: e1000154. PMID: 18688277, PMCID: PMC2483943, DOI: 10.1371/journal.pgen.1000154.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesBone DensityCalcification, PhysiologicCells, CulturedFibroblast Growth Factor-23Fibroblast Growth FactorsGene ExpressionHypophosphatemiaMiceMice, Inbred C57BLMice, KnockoutMuscle, SkeletalOsteoblastsPhenotypePhosphatesSerumSkullSodium-Phosphate Cotransporter Proteins, Type IIaUrineConceptsFGF-23 geneFgf-23-/- micePhosphate homeostasisGenetic evidenceFgf-23-/-Regulation of phosphate homeostasisCrucial biological importanceFirst genetic evidenceSystemic phosphate homeostasisSkeletal mineralizationCellular functionsDouble mutantNew mouse lineMaster regulatorProtein abundanceGenomic ablationMolecular mechanismsDouble mutant miceChondrocyte differentiationTargeted disruptionSkeletal phenotypeBiological importanceGenesEnergy metabolismHomeostasis
2004
Brittle IV Mouse Model for Osteogenesis Imperfecta IV Demonstrates Postpubertal Adaptations to Improve Whole Bone Strength*
Kozloff KM, Carden A, Bergwitz C, Forlino A, Uveges TE, Morris MD, Marini JC, Goldstein SA. Brittle IV Mouse Model for Osteogenesis Imperfecta IV Demonstrates Postpubertal Adaptations to Improve Whole Bone Strength*. Journal Of Bone And Mineral Research 2004, 19: 614-622. PMID: 15005849, DOI: 10.1359/jbmr.040111.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAgingAmino Acid SubstitutionAnatomy, Cross-SectionalAnimalsBone DensityBone DevelopmentBone MatrixCollagen Type IDisease Models, AnimalFemurMaleMiceMice, TransgenicMineralsOsteogenesis ImperfectaRadiographySpectrum Analysis, RamanStress, MechanicalTensile StrengthConceptsMatrix material propertiesWhole bone geometryMaterial propertiesWhole bone strengthOsteogenesis imperfectaMouse modelBone geometryBone strengthMatrix compositesMechanical testsStiffness increaseType IV osteogenesis imperfectaMicroCT dataInvestigate therapeutic interventionsGeometric parametersMechanism independent of changesMouse model of OIRaman spectroscopic resultsMonths of ageMechanically tested to failureKnock-in modelOI patientsRaman spectroscopyGeometric resistanceIndependent of changes
2001
Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells
Bergwitz C, Wendlandt T, Kispert A, Brabant G. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Biochimica Et Biophysica Acta 2001, 1538: 129-140. PMID: 11336784, DOI: 10.1016/s0167-4889(00)00123-3.Peer-Reviewed Original ResearchConceptsChondrogenic cell lineReporter gene expressionWnt effectsGene expressionCell linesWnt-7aChondrogenic differentiationWnt-5aGreen fluorescence proteinProtein kinase C.Protein kinase CFrizzled-related proteinsCollagen type II promoterLimb patterningSignal transductionEmbryonic developmentRat calvaria cellsWnt familyType II promoterNIH3T3 cellsReporter systemCartilage-specific proteoglycansFluorescence proteinCartilage differentiationKinase C.
1999
The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues
Pötter E, Bergwitz C, Brabant G. The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues. Endocrine Reviews 1999, 20: 207-239. PMID: 10204118, DOI: 10.1210/edrv.20.2.0362.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCadherin-catenin systemBeta-catenin/TCF4 complexComplex signal transduction pathwaysCell-cell adhesionNormal cell functionSignal transduction pathwaysLoss-of-functionRegulate cellular differentiationActivation of oncogenesEpigenetic mechanismsExtracellular modulatorsTransduction pathwaysTCF4 complexPosttranscriptional eventsCellular differentiationEndocrine tissuesIntracellular signalingGenetic mouse modelsProcess of tumorigenesisCadherin-cateninsSomatic gene mutationsPreservation of tissue integrityGene silencingCell adhesionC-Myc
1997
Cloning and characterization of the vitamin D receptor from Xenopus laevis.
Li Y, Bergwitz C, Jüppner H, Demay M. Cloning and characterization of the vitamin D receptor from Xenopus laevis. Endocrinology 1997, 138: 2347-53. PMID: 9165021, DOI: 10.1210/endo.138.6.5210.Peer-Reviewed Original ResearchMeSH KeywordsAgingAmino Acid SequenceAnimalsBase SequenceBone and BonesChickensCloning, MolecularDimerizationEmbryo, NonmammalianFemaleGene Expression Regulation, DevelopmentalHumansIntestine, SmallKidneyMiceMolecular Sequence DataOrgan SpecificityPolymerase Chain ReactionRatsReceptors, CalcitriolReceptors, Retinoic AcidRecombinant ProteinsRetinoic Acid Receptor alphaSequence Homology, Amino AcidSkinSpecies SpecificityXenopus laevisConceptsVitamin D response elementRat osteocalcin vitamin D response elementVitamin D receptorOsteocalcin vitamin D response elementLower vertebrate speciesMessenger RNA speciesHuman vitamin D receptorMouse retinoid X receptor alphaAmino acid residuesRetinoid X receptor alphaRat osteocalcin vitamin D responsive elementAmino acid levelsX receptor alphaVertebrate speciesRNA speciesMammalian cellsTransfected mammalian cellsXenopus developmentDependent transactivationD response elementNuclear receptor superfamilyXenopus tissuesDNA bindingIon homeostasisNorthern analysis