2021
FGF23 signalling and physiology.
Ho BB, Bergwitz C. FGF23 signalling and physiology. Journal Of Molecular Endocrinology 2021, 66: r23-r32. PMID: 33338030, PMCID: PMC8782161, DOI: 10.1530/jme-20-0178.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsConserved SequenceEvolution, MolecularFibroblast Growth Factor-23HomeostasisHumansPhosphatesSignal TransductionConceptsO-glycosylation of FGF23FGF23 signalingSubtilisin-like proprotein convertase furinSuppressing phosphate reabsorptionProprotein convertase furinPost-translationallyO-glycosylationIntact FGF23C-terminusGenetic activityPrevent proteolysisParacrine FGFsHigh-affinity binding sitesFibroblast growth factor 23Fruit flyActive intact FGF23Convertase furinChronic kidney diseaseFGF23 fragmentsGrowth factor 23Physiological roleEndocrine FGFsDihydroxyvitamin D synthesisHyperphosphatemic disordersIntestinal phosphate absorption
2020
Targeted FGFR Blockade for the Treatment of Tumor-Induced Osteomalacia
Hartley IR, Miller CB, Papadakis GZ, Bergwitz C, Del Rivero J, Blau JE, Florenzano P, Berglund JA, Tassone J, Roszko KL, Moran S, Gafni RI, Isaacs R, Collins MT. Targeted FGFR Blockade for the Treatment of Tumor-Induced Osteomalacia. New England Journal Of Medicine 2020, 383: 1387-1389. PMID: 32905668, PMCID: PMC7561341, DOI: 10.1056/nejmc2020399.Peer-Reviewed Original ResearchMeSH KeywordsAgedChondrosarcoma, MesenchymalDisease ProgressionFatal OutcomeFibroblast Growth Factor-23Fibroblast Growth FactorsHumansMaleMolecular Targeted TherapyNeoplasms, Connective TissueOsteomalaciaParaneoplastic SyndromesPhenylurea CompoundsPositron Emission Tomography Computed TomographyPyrimidinesReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1
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 miceEndocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules
Rose E, Lee D, Xiao E, Zhao W, Wee M, Cohen J, Bergwitz C. Endocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules. Scientific Reports 2019, 9: 8798. PMID: 31217461, PMCID: PMC6584732, DOI: 10.1038/s41598-019-45269-x.Peer-Reviewed Original ResearchConceptsDrosophila renal tubulesFly life spanGenetic ablationRNAi-mediated knockdownInorganic phosphate (Pi) homeostasisHigh-Pi mediumPi transportersAdult fliesControl of FGF signalingHigher speciesPi mediumInduces expressionMFS2FGF signalingExcretion of PiPhosphate homeostasisDrosophilaFly longevityEndocrine regulationHormone fibroblast growth factor 23Renal tubulesHormonal controlPi transportFibroblast growth factor 23Genetic overexpression
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 disordersOrganismsHereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy
Bergwitz C, Miyamoto KI. Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy. Pflügers Archiv - European Journal Of Physiology 2018, 471: 149-163. PMID: 30109410, DOI: 10.1007/s00424-018-2184-2.ChaptersConceptsElevated 1,25(OH)2D levelsHereditary hypophosphatemic ricketsHypophosphatemic ricketsActive vitamin D analoguesEnhanced intestinal calcium absorptionActive vitamin D analogsFibroblast growth factor 23Kidney stonesRare autosomal recessive disorderIntestinal calcium absorptionGrowth factor 23Risk of kidney stonesUrinary phosphate wastingDistal renal tubulesVitamin D analogsX-linked hypophosphatemiaAutosomal recessive disorderDevelopment of kidney stonesLoss-of-function mutationsSecondary hyperparathyroidismClinical presentationFactor 23Parathyroid hormoneBone lossCalcium absorption
2017
Response 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
FGF23 and Syndromes of Abnormal Renal Phosphate Handling
Bergwitz C, Jüppner H. FGF23 and Syndromes of Abnormal Renal Phosphate Handling. Advances In Experimental Medicine And Biology 2012, 728: 41-64. PMID: 22396161, PMCID: PMC5234086, DOI: 10.1007/978-1-4614-0887-1_3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAbnormalities, MultipleAnimalsFibroblast Growth Factor-23Fibroblast Growth FactorsHomeostasisHumansKidney DiseasesPhosphatesSyndromeConceptsLoss-of-function mutationsParathyroid hormoneAutosomal dominant hypophosphatemic ricketsDentin matrix protein 1Ecto-nucleotide pyrophosphatase/phosphodiesterase 1O-glycosylation of FGF23Hypophosphatemic ricketsAbnormal renal phosphate handlingImpaired O-glycosylationFibroblast growth factor 23Hormonal bone-parathyroid-kidney axisGrowth factor 23Serum phosphate levelsRenal phosphate excretionRenal phosphate handlingFamilial hyperphosphatemic tumoral calcinosisSodium-phosphate cotransporters NaPi-IIaHereditary hypophosphatemic ricketsHyperphosphatemic tumoral calcinosisIncreased serum phosphate levelsFunction mutationsPhosphate-regulating geneRare genetic disorderCotransporter NaPi-IIaDominant hypophosphatemic rickets
2011
Case 33-2011 — A 56-Year-Old Man with Hypophosphatemia
Bergwitz C, Collins MT, Kamath RS, Rosenberg AE. Case 33-2011 — A 56-Year-Old Man with Hypophosphatemia. New England Journal Of Medicine 2011, 365: 1625-1635. PMID: 22029985, PMCID: PMC4907641, DOI: 10.1056/nejmcpc1104567.Peer-Reviewed Original Research
2010
Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23
Bergwitz C, Jüppner H. Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23. Annual Review Of Medicine 2010, 61: 91-104. PMID: 20059333, PMCID: PMC4777331, DOI: 10.1146/annurev.med.051308.111339.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCalcitriolFibroblast Growth Factor-23Fibroblast Growth FactorsHomeostasisHumansParathyroid HormonePhosphatesPhosphorus Metabolism DisordersConceptsParathyroid hormoneDentin matrix protein 1Regulation of phosphate homeostasisVitamin DPhosphate homeostasisFibroblast growth factor 23Serum phosphorus levelsGrowth factor 23Renal phosphate excretionSecretion of FGF23Secretion of parathyroid hormoneSodium-phosphate cotransporters NaPi-IIaCotransporter NaPi-IIaIncreases renal phosphate excretionGenetically engineered miceRegulation of calcium homeostasisHomologies to endopeptidasesKidney axisMatrix protein 1Sodium-phosphate cotransporter NaPi-IIaFactor 23Serum phosphorusPhosphate excretionParathyroid glandsHormonal bone-parathyroid-kidney axis
2009
Defective O-Glycosylation due to a Novel Homozygous S129P Mutation Is Associated with Lack of Fibroblast Growth Factor 23 Secretion and Tumoral Calcinosis
Bergwitz C, Banerjee S, Abu-Zahra H, Kaji H, Miyauchi A, Sugimoto T, Jüppner H. Defective O-Glycosylation due to a Novel Homozygous S129P Mutation Is Associated with Lack of Fibroblast Growth Factor 23 Secretion and Tumoral Calcinosis. The Journal Of Clinical Endocrinology & Metabolism 2009, 94: 4267-4274. PMID: 19837926, PMCID: PMC2775647, DOI: 10.1210/jc.2009-0961.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsBase SequenceCalcinosisCarrier StateChlorocebus aethiopsCodonCOS CellsDNA PrimersExonsFibroblast Growth Factor-23Fibroblast Growth FactorsGlycosylationHomozygoteHumansHypophosphatemia, FamilialMolecular Sequence DataNeoplasmsPolymorphism, Single NucleotideProlineSerineConceptsExpression vectors encoding wild-typeSerine to prolineHomozygous mutationFraction of lysatesCOS-7 cellsGlycoprotein fractionDefective O-glycosylationMutant hormoneO-glycosylationProtein speciesExon 2Poor secretionCOS-7Western blot analysisGenetic causeCodon 129Hyperphosphatemic tumoral calcinosisMutationsWild-typeFGF23 mutationsAssociated with lackBlot analysisCarriers in vivoFibroblast growth factorLysatesDisorders of Phosphate Homeostasis and Tissue Mineralisation
Bergwitz C, Jüppner H. Disorders of Phosphate Homeostasis and Tissue Mineralisation. Endocrine Development 2009, 16: 133-156. PMID: 19494665, PMCID: PMC3810012, DOI: 10.1159/000223693.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCalcinosisChildFibroblast Growth Factor-23Genetic TestingHomeostasisHumansHyperphosphatemiaLithiasisMetabolism, Inborn ErrorsMineralsPhosphatesConceptsDisorders of phosphate homeostasisPhosphate homeostasisFibroblast growth factor 23Secretion of parathyroid hormoneAbnormal phosphate homeostasisDentin matrix protein 1Tissue mineralizationGrowth factor 23Co-receptor KlothoBone-kidney axisReabsorption of phosphateExpression of FGF23Renal proximal tubulesHomologies to endopeptidasesMatrix protein 1Phosphate-regulating geneCirculating phosphate concentrationClinical presentationFactor 23Parathyroid hormoneUDP-N-acetyl-alpha-D-galactosamineParathyroid glandsDiagnostic evaluationProximal tubulesD-galactosamine
2008
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