Featured Publications
Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia
Li X, Lozovatsky L, Tommasini S, Fretz J, Finberg K. Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia. Blood Advances 2023, 7: 5156-5171. PMID: 37417950, PMCID: PMC10480544, DOI: 10.1182/bloodadvances.2022009524.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsEndothelial cellsBone marrowBM sectionsFGF23 upregulationFibroblast growth factor 23Iron deficiencyElevated serum erythropoietinFGF23 promoter activityBM endothelial cellsGrowth factor 23Vitamin D metabolismIron deficiency anemiaSystemic iron deficiencyKnockout mice exhibitBone marrow sinusoidal endothelial cellsNormal iron balanceNonanemic controlsChronic anemiaFactor 23D metabolismEndothelial cell populationErythropoietin treatmentDeficiency anemiaMouse modelIL‐1β Drives Production of FGF‐23 at the Onset of Chronic Kidney Disease in Mice
McKnight Q, Jenkins S, Li X, Nelson T, Marlier A, Cantley LG, Finberg KE, Fretz JA. IL‐1β Drives Production of FGF‐23 at the Onset of Chronic Kidney Disease in Mice. Journal Of Bone And Mineral Research 2020, 35: 1352-1362. PMID: 32154933, PMCID: PMC7363582, DOI: 10.1002/jbmr.4003.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseOnset of CKDEarly chronic kidney diseaseFGF-23 expressionFGF-23Renal dysfunctionParathyroid hormoneIL-1βCongenital chronic kidney diseaseFGF-23 levelsSerum parathyroid hormoneGlomerular capillary tuftCongenital modelSerum phosphateIron bioavailabilitySystemic elevationVitamin DInflammatory cytokinesKidney diseaseEarly biomarkersIron statusMouse modelPhosphate imbalanceInitial upregulationCapillary tuft
2020
“Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor
Kale SD, Mehrkens BN, Stegman MM, Kastelberg B, Carnes H, McNeill RJ, Rizzo A, Karyala SV, Coutermarsh-Ott S, Fretz JA, Sun Y, Koff JL, Rajagopalan G. “Small” Intestinal Immunopathology Plays a “Big” Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor. Frontiers In Immunology 2020, 11: 1311. PMID: 32676080, PMCID: PMC7333770, DOI: 10.3389/fimmu.2020.01311.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronavirus InfectionsCOVID-19Cytokine Release SyndromeCytokinesHLA-DR3 AntigenInterferon-gammaInterleukin-17Intestine, SmallJanus Kinase InhibitorsLymphocyte ActivationMiceMice, KnockoutNitrilesPandemicsPneumonia, ViralPyrazolesPyrimidinesT-Lymphocytes, Helper-InducerConceptsSmall bowel pathologyMultiple organ dysfunctionIL-17A deficiencySmall intestinal immunopathologyCytokine release syndromeToxic shock syndromeBowel pathologyIntestinal immunopathologyRelease syndromeChimeric antigen receptor T-cell therapySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Immune check point inhibitorsHLA-DR3 transgenic miceRespiratory syndrome coronavirus 2HLA-DR3 miceIFN-γ deficiencyCheck point inhibitorsSyndrome coronavirus 2T-cell therapyJAK 1/2 inhibitorJanus kinase inhibitorSmall intestinal tissueCoronavirus disease 2019T cell activation
2019
Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression
Nelson T, Velazquez H, Troiano N, Fretz JA. Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression. Journal Of The American Society Of Nephrology 2019, 30: 1559-1572. PMID: 31405952, PMCID: PMC6727263, DOI: 10.1681/asn.2018070699.Peer-Reviewed Original ResearchConceptsCOX-2 expressionEarly B-cell factor 1COX-2Peripheral glomeruliProximal tubular massLineage cellsB cell factor 1Cell factor 1Factor 1Transcription factor early B cell factor 1Glomerular developmentCalcineurin/NFATRenal insufficiencyCell typesGlomerular cell typesGlomerular mesangiumHypoplastic kidneyTubular massFl/Knockout miceMetanephric developmentNFATc1 activationImpaired maturationMiceGlomeruli
2017
Bone marrow adipocytes
Horowitz MC, Berry R, Holtrup B, Sebo Z, Nelson T, Fretz JA, Lindskog D, Kaplan JL, Ables G, Rodeheffer MS, Rosen CJ. Bone marrow adipocytes. Adipocyte 2017, 6: 193-204. PMID: 28872979, PMCID: PMC5638373, DOI: 10.1080/21623945.2017.1367881.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBone marrow adipocytesBone marrowMarrow adipocytesDistinct adipose depotsAdipose tissue increasesWhole-body metabolismHuman bone marrowAdipose depotsAdipose tissueBeige adipocytesBody metabolismMarrowLittle functional significanceFunctional significanceAdipocytesCell populationsTissue increasesInduction signalRecent dataCellsAdipokines
2014
Early B Cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue
Gao H, Mejhert N, Fretz JA, Arner E, Lorente-Cebrián S, Ehrlund A, Dahlman-Wright K, Gong X, Strömblad S, Douagi I, Laurencikiene J, Dahlman I, Daub CO, Rydén M, Horowitz MC, Arner P. Early B Cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue. Cell Metabolism 2014, 19: 981-992. PMID: 24856929, PMCID: PMC4109056, DOI: 10.1016/j.cmet.2014.03.032.Peer-Reviewed Original ResearchAdipocytesAdipogenesisAdipose Tissue, WhiteAdiposityAnimalsCells, CulturedDiabetes MellitusDiet, High-FatFemaleGene ExpressionHumansHypertrophyInflammationInsulin ResistanceLipolysisMaleMiceMice, Inbred C57BLMice, KnockoutRNA InterferenceRNA, Small InterferingTrans-ActivatorsTumor Necrosis Factor-alpha
2011
Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling
Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, Horsley V. Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling. Cell 2011, 146: 761-771. PMID: 21884937, PMCID: PMC3298746, DOI: 10.1016/j.cell.2011.07.019.Peer-Reviewed Original ResearchConceptsAdipocyte lineage cellsStem cell nicheStem cell activityLineage cellsCell nicheSkin stem cell nichesStem cell functionEpithelial stem cell nicheStem cell activationEpithelial stem cell functionSkin stem cellsTissue homeostasisNiche cellsFunctional analysisAdipogenic cellsSkin homeostasisMammalian skinTransplantation experimentsStem cellsPrecursor cellsHair cyclingCell functionAdipocyte cellsNicheFunctional tissue
2010
Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse
Fretz JA, Nelson T, Xi Y, Adams DJ, Rosen CJ, Horowitz MC. Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse. Endocrinology 2010, 151: 1611-1621. PMID: 20172967, PMCID: PMC2850234, DOI: 10.1210/en.2009-0987.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAdipose TissueAnimalsBlood GlucoseBone MarrowCalorimetryCCAAT-Enhancer-Binding Protein-betaEnergy MetabolismGlucagonInsulinLeptinLipid MetabolismLipodystrophyMiceMice, KnockoutPPAR gammaReverse Transcriptase Polymerase Chain ReactionRNA, MessengerStatistics, NonparametricTrans-ActivatorsConceptsSerum glucose levelsWhite adipose tissueMarrow adiposityGlucose levelsAdipose tissueLevels of leptinBone formation rateAdipose tissue depositionNumber of osteoblastsWk of ageAltered bone morphologySerum osteocalcinInsulin levelsGlucose challengeIP injectionPancreatic hormonesLittermate controlsLipid depositionBone marrowSerum analysisBrown adiposeTissue depositionAltered metabolismMiceAdiposity
2009
Regulation of Aryl Hydrocarbon Receptor Function by Selective Estrogen Receptor Modulators
DuSell CD, Nelson ER, Wittmann BM, Fretz JA, Kazmin D, Thomas RS, Pike JW, McDonnell DP. Regulation of Aryl Hydrocarbon Receptor Function by Selective Estrogen Receptor Modulators. Endocrinology 2009, 24: 33-46. PMID: 19901195, PMCID: PMC2802893, DOI: 10.1210/me.2009-0339.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorBreast NeoplasmsCell DifferentiationCell LineCell Line, TumorChromatin ImmunoprecipitationDose-Response Relationship, DrugFemaleGene Expression ProfilingGene Expression RegulationHumansMaleMiceOsteoclastsReceptors, Aryl HydrocarbonReceptors, EstrogenRecombinant ProteinsSelective Estrogen Receptor ModulatorsTamoxifenConceptsSelective estrogen receptor modulatorsAryl hydrocarbon receptorEstrogen receptor modulatorsEstrogen receptorReceptor modulatorsBreast cancerAbsence of ERER-independent mannerAryl hydrocarbon receptor functionAgonist/antagonist activityActivity of drugsAhR target genesEstradiol metabolismPharmacological actionsOsteoclast differentiationTamoxifenTherapeutic efficacyActive metaboliteReceptor functionAntagonist activityHydrocarbon receptorCalcium signalingCellular proliferationPotential roleCellular model
2008
Ebf1-dependent control of the osteoblast and adipocyte lineages
Hesslein DG, Fretz JA, Xi Y, Nelson T, Zhou S, Lorenzo JA, Schatz DG, Horowitz MC. Ebf1-dependent control of the osteoblast and adipocyte lineages. Bone 2008, 44: 537-546. PMID: 19130908, PMCID: PMC2657874, DOI: 10.1016/j.bone.2008.11.021.Peer-Reviewed Original ResearchConceptsNumber of osteoclastsBone formation parametersBone formation rateAdipocyte lineageBone marrow cellsOlfactory sensory neuronsSerum osteocalcinOsteoid volumeSensory neuronsAdipocyte numberBone marrowOsteoclast developmentMutant miceMarrow cellsMiceSubcutaneous sitesBone formationAdipocyte developmentStriking increaseDecreased depositionTranscription factorsOsteoblastsB cell fate specificationEBF1Adiposity
2007
Receptor Activator of Nuclear Factor-κB Ligand-Induced Nuclear Factor of Activated T Cells (C1) Autoregulates Its Own Expression in Osteoclasts and Mediates the Up-Regulation of Tartrate-Resistant Acid Phosphatase
Fretz JA, Shevde NK, Singh S, Darnay BG, Pike JW. Receptor Activator of Nuclear Factor-κB Ligand-Induced Nuclear Factor of Activated T Cells (C1) Autoregulates Its Own Expression in Osteoclasts and Mediates the Up-Regulation of Tartrate-Resistant Acid Phosphatase. Endocrinology 2007, 22: 737-750. PMID: 18063694, PMCID: PMC2262172, DOI: 10.1210/me.2007-0333.Peer-Reviewed Original ResearchMeSH KeywordsAcid PhosphataseAnimalsBlotting, WesternBone and BonesCell LineChromatin ImmunoprecipitationHomeostasisIsoenzymesMiceMice, Inbred C57BLNFATC Transcription FactorsOsteoclastsPromoter Regions, GeneticRANK LigandReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTartrate-Resistant Acid PhosphataseTranscription, GeneticUp-RegulationConceptsNFAT membersRNA polymerase IIDNA-binding proteinsSpecific transcription factorsChromatin immunoprecipitation analysisSignal transduction pathwaysAdditional molecular detailsNuclear factorActivated T cells cytoplasmic 1Polymerase IIAcp5 promotersTranscription factorsTransduction pathwaysMolecular detailsTarget genesOwn expressionImmunoprecipitation analysisP1 promoterBone-resorbing cellsReceptor activatorHematopoietic precursorsGenesNuclear factor-κB ligandCytoplasmic 1Time-dependent accumulationTargeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-κB Ligand Gene Reduces Bone Remodeling and Increases Bone Mass
Galli C, Zella LA, Fretz JA, Fu Q, Pike JW, Weinstein RS, Manolagas SC, O’Brien C. Targeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-κB Ligand Gene Reduces Bone Remodeling and Increases Bone Mass. Endocrinology 2007, 149: 146-153. PMID: 17932217, PMCID: PMC2194617, DOI: 10.1210/en.2007-0734.Peer-Reviewed Original Research1,25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene's transcriptional start site
Fretz JA, Zella LA, Kim S, Shevde NK, Pike JW. 1,25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene's transcriptional start site. The Journal Of Steroid Biochemistry And Molecular Biology 2007, 103: 440-445. PMID: 17229572, PMCID: PMC1868540, DOI: 10.1016/j.jsbmb.2006.11.018.Peer-Reviewed Original ResearchConceptsTranscriptional start siteGene transcriptional start siteChIP-chip analysisLRP5/LRP6Chromatin structureHuman genomeRegulatory regionsStart siteRegulatory elementsWnt familyHeterologous promoterCanonical WntMembrane receptorsMRNA transcriptsWntSecreted memberOsteoblastic cellsLRP5GenesVDRELRP5 geneBone formationProteinLrp5 locusOsteoblast numberPerspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor
Pike JW, Meyer MB, Watanuki M, Kim S, Zella LA, Fretz JA, Yamazaki M, Shevde NK. Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor. The Journal Of Steroid Biochemistry And Molecular Biology 2007, 103: 389-395. PMID: 17223545, PMCID: PMC1868541, DOI: 10.1016/j.jsbmb.2006.12.050.Peer-Reviewed Original ResearchConceptsTarget genesBasal transcriptional machineryChromatin immunoprecipitation techniqueVitamin D receptorKey target genesExpression of genesAltered gene expressionTranscriptional machineryVertebrate organismsGene regulationSystemic signalsTranscriptional modulationRegulatory regionsDNA sitesGene locusGene expressionPromoter regionEnhancer regionGenesImmunoprecipitation techniquesRegulatory capabilitiesMaintenance of calciumModular natureExpressionNew insightsMultiple enhancer regions located at significant distances upstream of the transcriptional start site mediate RANKL gene expression in response to 1,25-dihydroxyvitamin D3
Kim S, Yamazaki M, Zella LA, Meyer MB, Fretz JA, Shevde NK, Pike JW. Multiple enhancer regions located at significant distances upstream of the transcriptional start site mediate RANKL gene expression in response to 1,25-dihydroxyvitamin D3. The Journal Of Steroid Biochemistry And Molecular Biology 2007, 103: 430-434. PMID: 17197168, PMCID: PMC1892901, DOI: 10.1016/j.jsbmb.2006.12.020.Peer-Reviewed Original ResearchConceptsTranscription start siteStart siteChip analysisMultiple enhancer regionsRNA polymerase IIPotential regulatory regionsTranscriptional start siteRANKL geneVDR/RXRChromatin hubHistone modificationsTranscriptional outputPolymerase IIRANKL gene expressionImportant functional consequencesMultiple enhancersRegulatory regionsTranscription factorsHeterologous promoterGene locusEnhancer regionGene expressionKb upstreamRANKL promoterLuciferase assay
2006
1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence elements located downstream of the start site of transcription.
Fretz JA, Zella LA, Kim S, Shevde NK, Pike JW. 1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence elements located downstream of the start site of transcription. Endocrinology 2006, 20: 2215-30. PMID: 16613987, DOI: 10.1210/me.2006-0102.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone and BonesCells, CulturedChromatinChromatin ImmunoprecipitationConserved SequenceDimerizationDNAGene Expression RegulationHumansIntronsLDL-Receptor Related ProteinsLow Density Lipoprotein Receptor-Related Protein-5MiceMice, Inbred C57BLMolecular Sequence DataOsteoblastsPromoter Regions, GeneticProtein BindingReceptors, CalcitriolRetinoid X ReceptorsRNA Polymerase IISequence AlignmentTranscription, GeneticVitamin DVitamin D Response ElementConceptsVitamin D response elementD response elementResponse elementDNA microarray analysisChromatin structureChromatin immunoprecipitationOsteoblast biologyReceptor FrizzledHuman genomeLipoprotein receptor-related protein 5Regulatory regionsStart siteLrp5 locusLow-density lipoprotein receptor-related protein 5Sequence elementsHeterologous promoterMature osteoblastsMicroarray analysisOsteoblast precursorsDirect targetProtein 5Cell line originLine originPrimary osteoblastsGenes