2024
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution
Jeong J, Lee J, Talaia G, Kim W, Song J, Hong J, Yoo K, Gonzalez D, Athonvarangkul D, Shin J, Dann P, Haberman A, Kim L, Ferguson S, Choi J, Wysolmerski J. Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution. Cellular And Molecular Life Sciences 2024, 81: 29. PMID: 38212474, PMCID: PMC10784359, DOI: 10.1007/s00018-023-05044-8.Peer-Reviewed Original Research
2022
PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development
Grinman DY, Boras-Granic K, Takyar FM, Dann P, Hens JR, Marmol C, Lee J, Choi J, Chodosh LA, Sola MEG, Wysolmerski JJ. PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development. Breast Cancer Research 2022, 24: 30. PMID: 35440032, PMCID: PMC9020078, DOI: 10.1186/s13058-022-01523-1.Peer-Reviewed Original ResearchConceptsOverexpression of PTHrPSecretory differentiationEpithelial cellsPTHrP overexpressionTumor latencyBreast cancerMammary epithelial cellsType 1 PTH/PTHrP receptorMMTV-PyMT breast cancer modelPTH/PTHrP receptorMMTV-PyMT miceMammary tumor developmentBreast cancer riskBreast cancer biologyExpression of PTHrPHormone-related proteinHuman breast cancerBreast cancer modelE74-like factor 5Normal mammary epithelial cellsBreast cancer progressionMouse mammary tumorsExpression of markersAlveolar epithelial cellsLuminal epithelial cells
2019
Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Lotinun S, Ishihara Y, Nagano K, Kiviranta R, Carpentier VT, Neff L, Parkman V, Ide N, Hu D, Dann P, Brooks D, Bouxsein ML, Wysolmerski J, Gori F, Baron R. Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression. Journal Of Clinical Investigation 2019, 129: 3058-3071. PMID: 31112135, PMCID: PMC6668688, DOI: 10.1172/jci122936.Peer-Reviewed Original ResearchConceptsLactation-induced bone lossParathyroid hormoneBone lossBone resorptionCathepsin KMilk calcium levelsParathyroid hormone suppressionSerum parathyroid hormoneRegulation of PTHOsteoclastic bone resorptionTrabecular bone volumeOsteocyte lacunar areaHormone suppressionHigh calcium demandOsteoclast numberCortical thicknessEffect of lactationCalcium levelsNormal rangeBone volumeCalcium demandExact mechanismLacunar areaResorptionSufficient calciumNHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland
Jeong J, Kim W, Hens J, Dann P, Schedin P, Friedman PA, Wysolmerski JJ. NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland. Endocrinology 2019, 160: 1797-1810. PMID: 31087002, PMCID: PMC6619491, DOI: 10.1210/en.2019-00230.Peer-Reviewed Original ResearchConceptsPlasma membrane calcium ATPase 2Mammary epithelial cellsSpecialized plasma membrane domainsMammary epithelial cell deathLuminal epithelial cellsCell deathPremature mammary gland involutionBreast cancer cellsApical-basal polarityEpithelial cellsPlasma membrane domainsApical membraneSecretory luminal epithelial cellsExchanger regulatory factor 1Cell death pathwaysNHERF1 expressionMammary gland involutionCancer cellsRegulatory factor 1Sodium-hydrogen exchanger regulatory factor-1Lactating Mammary GlandNormal mammary epithelial cellsMembrane localizationEpithelial cell deathMembrane domains
2018
Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nature Communications 2018, 9: 3592. PMID: 30181538, PMCID: PMC6123393, DOI: 10.1038/s41467-018-05911-0.Peer-Reviewed Original ResearchConceptsMouse mammary glandMilk-producing epithelial cellsTissue-specific rolesMammary glandAdipose growthLipid dynamicsGenetic tracingPhysiological examplesFunctional implicationsCellular mechanismsAdipocyte hypertrophyMature adipocytesEssential roleVivo analysisTissue functionMammary epitheliumAdipocytesEpithelial cellsAdipocyte precursorsSubsequent involutionMilk lipidsPrimary mechanismMechanismLipidomicsMilk fat production
2015
OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism
Ardeshirpour L, Dumitru C, Dann P, Sterpka J, VanHouten J, Kim W, Kostenuik P, Wysolmerski J. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism. Endocrinology 2015, 156: 2762-2773. PMID: 25961842, PMCID: PMC4511126, DOI: 10.1210/en.2015-1232.Peer-Reviewed Original ResearchConceptsBone lossOPG treatmentOsteoblast numberActivated B cells ligandLactational bone lossMaternal calcium homeostasisMaternal calcium metabolismMilk calcium levelsRapid bone lossDietary calcium intakeMaternal bone lossBone resorption rateMaternal hypocalcemiaRecombinant OPGCalcium intakeMaternal deathsOsteoprotegerin levelsMaternal skeletonBone turnoverDietary calciumCalcium metabolismOsteoclast numberBone massOsteoclast activityAnabolic response
2013
Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual
Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, Wysolmerski J. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual. Endocrinology 2013, 154: 3031-3042. PMID: 23782944, PMCID: PMC3749485, DOI: 10.1210/en.2012-2195.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiological TransportBone DevelopmentBone ResorptionCalciumCrosses, GeneticFemaleGene Expression RegulationLactationLactoglobulinsMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMilkParathyroid HormoneParathyroid Hormone-Related ProteinReceptors, Calcium-SensingRNA, MessengerConceptsRenal calcium excretionCalcium excretionCalcium metabolismBone resorptionCalcium transportMilk calciumMammary glandAccelerated bone resorptionMammary-specific ablationMaternal calcium metabolismDietary calcium intakeCalcium sensing receptorCalcium-sensing receptorSecretion of PTHrPSkeletal calcium storesMilk PTHrPCalcium intakePTH secretionPTHrP secretionMaternal boneBone turnoverBone metabolismOnset of lactationMaternal circulationSystemic calciumThe calcium-sensing receptor in the breast
VanHouten JN, Wysolmerski JJ. The calcium-sensing receptor in the breast. Best Practice & Research Clinical Endocrinology & Metabolism 2013, 27: 403-414. PMID: 23856268, PMCID: PMC3713417, DOI: 10.1016/j.beem.2013.02.011.BooksConceptsG-protein usageBreast cancer cellsCalcium-sensing receptorCalcium metabolismCancer cellsParathyroid hormone-related protein levelsBreast cellsMaternal calcium metabolismOsteolytic skeletal metastasesSystemic calcium metabolismEpithelial cellsNormal breast epithelial cellsFeed-forward cycleMalignant breast cellsNormal breast cellsBreast epithelial cellsSkeletal metastasesPTHrP productionPTHrP expressionMammary epithelial cellsCaSRCalcium transportProtein levelsTransport of calciumSupply of calciumOsteocytes remove and replace perilacunar mineral during reproductive cycles
Wysolmerski JJ. Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone 2013, 54: 230-236. PMID: 23352996, PMCID: PMC3624069, DOI: 10.1016/j.bone.2013.01.025.BooksConceptsBone lossLevels of PTHrPNegative calcium balanceLevels of estrogenPrincipal bone-resorbing cellsSkeletal calcium storesBone-resorbing cellsPTHrP levelsBone turnoverBone resorptionBone massMineral metabolismCalcium balanceRole of osteocytesCalcium storesMineral homeostasisOsteocytic osteolysisReproductive cycleOsteocytesSystemic demandsPericanalicular matrixCalciumLactationBone
2012
Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation
Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jähn K, Kato S, Wysolmerski J, Bonewald LF. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. Journal Of Bone And Mineral Research 2012, 27: 1018-1029. PMID: 22308018, PMCID: PMC3770147, DOI: 10.1002/jbmr.1567.Peer-Reviewed Original Research
2011
Site‐specific changes in bone microarchitecture, mineralization, and stiffness during lactation and after weaning in mice
Liu XS, Ardeshirpour L, VanHouten JN, Shane E, Wysolmerski JJ. Site‐specific changes in bone microarchitecture, mineralization, and stiffness during lactation and after weaning in mice. Journal Of Bone And Mineral Research 2011, 27: 865-875. PMID: 22189918, DOI: 10.1002/jbmr.1503.Peer-Reviewed Original ResearchConceptsWhole bone stiffnessNulliparous miceBone microarchitectureTissue mineralizationBone mineral density BMDIndividual trabecula segmentationDramatic bone lossBone mineral densityBone stiffnessRecovered miceBone lossMineral densityPup weaningEffect of lactationMouse modelSkeletal sitesBone quantityClinical observationsMicro-finite element analysisBone qualitySite-specific changesSkeletal changesDigital topological analysisMiceCortical structuresParathyroid Hormone-Related Protein Is Not Required for Normal Ductal or Alveolar Development in the Post-Natal Mammary Gland
Boras-Granic K, VanHouten J, Hiremath M, Wysolmerski J. Parathyroid Hormone-Related Protein Is Not Required for Normal Ductal or Alveolar Development in the Post-Natal Mammary Gland. PLOS ONE 2011, 6: e27278. PMID: 22087279, PMCID: PMC3210770, DOI: 10.1371/journal.pone.0027278.Peer-Reviewed Original ResearchConceptsMammary glandPTHrP expressionAlveolar developmentMyoepithelial cellsMaternal calcium homeostasisOverexpression of PTHrPRole of PTHrPExpression of PTHrPEmbryonic mammary budPTHrP deficiencyMouse mammary glandParathyroid hormoneTransgenic miceDuctal developmentCalcium homeostasisAlveolar cellsPTHrPPubertal developmentMMTV-CrePost-natal mammary glandMammary developmentMammary budPostnatal mammary glandCre transgenePTHrP geneSkeletal recovery after weaning does not require PTHrP*
Kirby BJ, Ardeshirpour L, Woodrow JP, Wysolmerski JJ, Sims NA, Karaplis AC, Kovacs CS. Skeletal recovery after weaning does not require PTHrP*. Journal Of Bone And Mineral Research 2011, 26: 1242-1251. PMID: 21308774, PMCID: PMC3179289, DOI: 10.1002/jbmr.339.Peer-Reviewed Original ResearchConceptsBone mineral contentParathyroid hormoneBone massSerum calciumLumbar spine bone mineral contentTrabecular bone mineral contentParathyroid hormone-related proteinSpine bone mineral contentBone formationNormal serum calciumLow bone massAdult bone massPTHrP mRNA expressionWild-type miceHormone-related proteinEnd of lactationType 1 collagenUrine calciumSkeletal recoveryPTHrP mRNANull miceMRNA expressionFull recoveryMiceConditional knockout
2010
Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton
Ardeshirpour L, Brian S, Dann P, VanHouten J, Wysolmerski J. Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton. Endocrinology 2010, 151: 5591-5601. PMID: 21047946, PMCID: PMC2999486, DOI: 10.1210/en.2010-0566.Peer-Reviewed Original ResearchConceptsBone mineral densityBone lossEstrogen deficiencyMineral densityInfusion of PTHrPReversible bone lossLevels of estrogenCombination of OVXLeuprolide treatmentCentral hypogonadismGnRH agonistMaternal skeletonBone turnoverOsmotic minipumpsOsteoclast numberBone metabolismBone resorptionSurgical ovariectomyNulliparous micePTHrPOVXInfusionEstrogenLeuprolideModest declineInteractions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation
Wysolmerski JJ. Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation. Annals Of The New York Academy Of Sciences 2010, 1192: 161-169. PMID: 20392232, PMCID: PMC3777748, DOI: 10.1111/j.1749-6632.2009.05249.x.BooksCharacterization of the Six1 homeobox gene in normal mammary gland morphogenesis
Coletta RD, McCoy EL, Burns V, Kawakami K, McManaman JL, Wysolmerski JJ, Ford HL. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC Developmental Biology 2010, 10: 4. PMID: 20074369, PMCID: PMC2823684, DOI: 10.1186/1471-213x-10-4.Peer-Reviewed Original ResearchConceptsNormal mammary gland developmentAdult mammary glandMammary gland developmentMammary glandMammary developmentBreast cancerMouse modelBreast tumorigenesisEmbryonic mammary glandPostnatal mammary developmentRag1-/- miceNormal mammary gland morphogenesisGland developmentTransgenic mouse modelBreast cancer initiationViable therapeutic targetIndependent mouse modelsAdult mouse mammary glandAnti-cancer therapyMammary stem cellsFamily membersMouse mammary glandUnwanted side effectsRole of Six1Invasive carcinoma
2008
Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*
Mamillapalli R, VanHouten J, Zawalich W, Wysolmerski J. Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*. Journal Of Biological Chemistry 2008, 283: 24435-24447. PMID: 18621740, PMCID: PMC2528989, DOI: 10.1074/jbc.m801738200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone NeoplasmsBreast NeoplasmsCell Line, TumorCyclic AMPCyclic AMP-Dependent Protein KinasesFemaleGTP-Binding Protein alpha SubunitsHumansHypercalcemiaLactationMammary Glands, AnimalMammary Neoplasms, AnimalMAP Kinase Signaling SystemMiceNeoplasm MetastasisNeoplasm ProteinsParathyroid Hormone-Related ProteinPregnancyReceptors, Calcium-SensingType C PhospholipasesConceptsG-protein usagePTHrP productionMammary epithelial cellsBreast cancer cellsBreast cellsMCF-7 cellsParathyroid hormone-related protein secretionParathyroid hormone-related proteinParathyroid hormone secretionCancer cellsMCF-7 human breast cancer cellsCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinNormal mammary epithelial cellsRegulation of calciumMalignant breast cellsNormal breast cellsG protein-coupled receptorsG protein couplingBone metastasesPTHrP secretionHormone secretionBone metabolismBreast cancer
2007
The Calcium-Sensing Receptor Regulates Plasma Membrane Calcium Adenosine Triphosphatase Isoform 2 Activity in Mammary Epithelial Cells: A Mechanism for Calcium-Regulated Calcium Transport into Milk
VanHouten JN, Neville MC, Wysolmerski JJ. The Calcium-Sensing Receptor Regulates Plasma Membrane Calcium Adenosine Triphosphatase Isoform 2 Activity in Mammary Epithelial Cells: A Mechanism for Calcium-Regulated Calcium Transport into Milk. Endocrinology 2007, 148: 5943-5954. PMID: 17823248, PMCID: PMC7108505, DOI: 10.1210/en.2007-0850.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportBlotting, WesternCalciumCells, CulturedEpithelial CellsFemaleFluorescent Antibody TechniqueGadoliniumIsoenzymesLactationMammary Glands, AnimalMiceMice, Inbred BALB CMicroscopy, ImmunoelectronMilkMilk ProteinsMutationOligonucleotide Array Sequence AnalysisPlasma Membrane Calcium-Transporting ATPasesReceptors, Calcium-SensingReverse Transcriptase Polymerase Chain ReactionConceptsPlasma membrane calcium ATPase isoform 2Mammary epithelial cellsMouse mammary epithelial cellsEpH4 mouse mammary epithelial cellsEpithelial cellsGenome-wide screening strategyApical plasma membraneATPase activityPotential downstream targetsATPase isoform 2Mouse mammary glandPlasma membrane preparationsDeafwaddler miceTransepithelial calcium transportPlasma membraneDownstream targetsGene knockdownPMCA2 activityCalcium transportIsoform 2Calcium-dependent ATPase activityCell membraneCultured primaryCalcium-sensing receptorPMCA2 expressionWeaning Triggers a Decrease in Receptor Activator of Nuclear Factor-κB Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice
Ardeshirpour L, Dann P, Adams DJ, Nelson T, VanHouten J, Horowitz MC, Wysolmerski JJ. Weaning Triggers a Decrease in Receptor Activator of Nuclear Factor-κB Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice. Endocrinology 2007, 148: 3875-3886. PMID: 17495007, DOI: 10.1210/en.2006-1467.Peer-Reviewed Original ResearchConceptsBone lossBone massBone turnoverReceptor activatorOsteoclast apoptosisRapid bone lossC-telopeptide levelsNumber of osteoclastsBone formation rateNuclear factor-kappaB ligand (RANKL) mRNANuclear factor-kappaB ligand (RANKL) expressionRapid recoveryLevels of osteocalcinCessation of lactationSkeletal anabolismPTH levelsCalcium metabolismBone resorptionBone histomorphometryBone microarchitectureCalcium levelsOsteoblast numberLigand expressionReciprocal decreaseBone recovery
2005
The calcium-sensing receptor regulates PTHrP production and calcium transport in the lactating mammary gland
Ardeshirpour L, Dann P, Pollak M, Wysolmerski J, VanHouten J. The calcium-sensing receptor regulates PTHrP production and calcium transport in the lactating mammary gland. Bone 2005, 38: 787-793. PMID: 16377269, DOI: 10.1016/j.bone.2005.11.009.Peer-Reviewed Original ResearchConceptsCalcium-sensing receptorPTHrP productionMammary epithelial cellsMammary glandCalcium transportEpithelial cellsCalcium homeostasisParathyroid hormone-related proteinParathyroid hormone secretionProduction of PTHrPHormone-related proteinSystemic calcium homeostasisExtracellular calcium ionsTransepithelial calcium transportG protein-coupled receptorsHormone secretionParathyroid glandsBone massCalcium handlingRenal tubulesTransient lossGlandGenetic confirmationReceptorsSecretion