Featured Publications
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetTreating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation
Kwon HK, Dussik CM, Kim SH, Kyriakides TR, Oh I, Lee FY. Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation. Frontiers In Cellular And Infection Microbiology 2022, 12: 897291. PMID: 35755835, PMCID: PMC9218192, DOI: 10.3389/fcimb.2022.897291.Peer-Reviewed Original ResearchConceptsSeptic arthritisBacterial burdenAntibiotic treatmentMurine modelTherapeutic goalsConcurrent antimicrobial therapyDistinct therapeutic goalsGeneration of inflammationMRSA septic arthritisSeptic knee arthritisInflammatory joint conditionsArticular cartilageMitigation of inflammationPost-antibiotic treatmentNovel therapeutic strategiesSeptic arthritis modelArticular cartilage damageEx vivo modelArticular cartilage integrityInflammatory arthritisInhibitors of ERKInflammatory profileMRSA infectionSynovial tissueExcessive inflammationEnhancement of Impaired MRSA‐Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation
Yu KE, Kwon H, Dussik CM, Cahill SV, Back J, Alder KD, Lee FY. Enhancement of Impaired MRSA‐Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation. Journal Of Bone And Mineral Research 2020, 37: 1352-1365. PMID: 35616626, DOI: 10.1002/jbmr.4570.Peer-Reviewed Original ResearchConceptsMethicillin-resistant Staphylococcus aureusExcessive inflammationAntibiotic treatmentFracture healingTrametinib therapyInfected fracturesPro-inflammatory cytokine levelsPostoperative antibiotic administrationSetting of infectionMale C57BL/6 miceSystemic antibiotic treatmentAdjunctive therapeutic agentMRSA-infected miceImpaired callus formationFemoral fracture modelTherapeutic cohortCytokine levelsMRSA infectionMusculoskeletal infectionsPostoperative intervalsSystemic vancomycinAntibiotic administrationCytokine analysisC57BL/6 miceIntramedullary nailingConstruction and evaluation of a clinically relevant model of septic arthritis
Kwon H, Yu K, Lee F. Construction and evaluation of a clinically relevant model of septic arthritis. Lab Animal 2022, 52: 11-26. PMID: 36564668, DOI: 10.1038/s41684-022-01089-7.Peer-Reviewed Original ResearchConceptsSeptic arthritisAnimal modelsMethicillin-resistant Staphylococcus aureus culturesIntra-articular inflammationReproducible animal modelRelevant mouse modelExperimental animal modelsMRSA infectionCartilage destructionC57BL/6J miceInflammatory pathologyJoint diseaseTherapeutic medicationsMouse modelArthritisSynovial fluidClinical relevancePotential treatmentHuman patientsKnee jointDirect inoculationAureus culturesMRSAMiceStaphylococcus aureus culturesDual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis
Kwon HK, Lee I, Yu KE, Cahill SV, Alder KD, Lee S, Dussik CM, Back J, Choi J, Song L, Kyriakides TR, Lee FY. Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis. Science Advances 2021, 7: eabf2665. PMID: 34172438, PMCID: PMC8232912, DOI: 10.1126/sciadv.abf2665.Peer-Reviewed Original ResearchConceptsIntra-articular inflammationSeptic arthritisBacterial infectionsDual therapeutic targetingKnee septic arthritisPromising new therapeutic strategyArticular cartilageChallenging clinical problemNovel treatment modalitiesIntracellular bacteriaNew therapeutic strategiesAdjuvant targetingTreatment modalitiesBacterial eradicationSuccessful treatmentHost inflammationCausative bacteriaMurine modelTherapeutic strategiesArthritisTherapeutic goalsClinical problemTherapeutic targetingInflammationVital organsBiocompatibility of platinum-based bulk metallic glass in orthopedic applications
Loye AM, Kwon HK, Dellal D, Ojeda R, Lee S, Davis R, Nagle N, Doukas PG, Schroers J, Lee FY, Kyriakides TR. Biocompatibility of platinum-based bulk metallic glass in orthopedic applications. Biomedical Materials 2021, 16: 045018. PMID: 33873168, DOI: 10.1088/1748-605x/abf981.Peer-Reviewed Original ResearchConceptsBulk metallic glassPt-BMGPlatinum-based bulk metallic glassMetallic glassesConventional metallic implantsCorrosion resistanceHigh strengthMechanical testingOrthopedic applicationsBone applicationsMetallic implantsMicro-computed tomographyAmorphous metalsTitaniumWearBiocompatibilitySimilar biocompatibilityFurther processingGlassDuctilityNanopatternsNanoscaleApplicationsMesenchymal stem cellsStrengthSmoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains
Hao Z, Li J, Li B, Alder KD, Cahill SV, Munger AM, Lee I, Kwon H, Back J, Xu S, Kang M, Lee FY. Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains. Journal Of Bone And Mineral Research 2020, 36: 186-198. PMID: 32866293, PMCID: PMC9057220, DOI: 10.1002/jbmr.4175.Peer-Reviewed Original ResearchConceptsCigarette smoke exposureCigarette smokingFracture healingSmoke exposureMurine modelMolecular alterationsBALB/cJ miceBiomechanical testingPro-inflammatory mediatorsCytokine/chemokine analysisImpaired fracture healingMultiplex cytokine/chemokine analysisInitial inflammatory responseFracture healing capacityBALB/cJProgenitor cell activitySmoking miceTransverse femoral osteotomyFemoral osteotomyImmune cellsChemokine analysisInflammatory responseFracture hematomaHigh riskMurine strains
2024
Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report
Jiang W, Caruana D, Back J, Lee F. Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report. Cells 2024, 13: 522. PMID: 38534368, PMCID: PMC10969736, DOI: 10.3390/cells13060522.Peer-Reviewed Original ResearchConceptsMDA-MB-231Transcriptomic platformsGene expressionSpatially localized gene expressionMDA-MB-231 metastatic breast cancer cellsSpatial transcriptomics platformGenetic expression changesFracture healingMetastatic breast cancer cellsBreast cancer cellsImpaired fracture healingSingle-cell RNALocal gene expressionSpatial transcriptomic profilingFracture callus formationGenomic heterogeneitySequencing techniquesDisrupt bone homeostasisTranscriptome profilingIn situ hybridizationExpression changesSoft callusPathological fracturesWild-typeSpatial transcriptomics
2023
Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model
Kwon H, Cahill S, Yu K, Alder K, Dussik C, Jeong J, Back J, Lee F. Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model. Frontiers In Cellular And Infection Microbiology 2023, 13: 1230568. PMID: 37829606, PMCID: PMC10565816, DOI: 10.3389/fcimb.2023.1230568.Peer-Reviewed Original ResearchConceptsFracture healingTeriparatide treatmentType 2 diabetic mouse modelType 2 diabetes mellitus miceBone volume/total volumeMurine diabetic modelTotal mineral densityIntermittent parathyroid hormoneSystemic antibiotic therapyImpairs fracture healingPoor fracture healingAdjuvant therapeutic agentDiabetes mellitus miceDiabetic mouse modelBlood glucose levelsCombination of antibioticsRadiographic union scaleTibia fracture modelIPTH treatmentSeptic nonunionNondiabetic counterpartsT2DM miceHormone therapyAntibiotic therapyMRSA infection
2019
A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice
Kwon HK, Patra MC, Shin HJ, Gui X, Achek A, Panneerselvam S, Kim DJ, Song SJ, Hong R, Kim KS, Kim YG, Lee FY, Hahm DH, Lee SH, Choi S. A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice. Experimental & Molecular Medicine 2019, 51: 1-19. PMID: 31028244, PMCID: PMC6486608, DOI: 10.1038/s12276-019-0244-0.Peer-Reviewed Original ResearchConceptsToll-like receptorsCollagen-induced arthritisInflammatory diseasesRodent modelsOverexpression of TLRsMultiple Toll-like receptorsAutoimmune/inflammatory diseasesSecretion of lipopolysaccharideDamage-associated molecular patternsInflammatory signaling cascadesIL-1β secretionNumerous inflammatory diseasesRheumatoid arthritisProinflammatory cytokinesLiver damageTLR4 TIR domainImmune responseAnimal studiesTherapeutic potentialToll/interleukinMolecular patternsMRNA levelsDiseaseArthritisSelective inhibitor
2017
Calreticulin inhibits inflammation‐induced osteoclastogenesis and bone resorption
Fischer CR, Mikami M, Minematsu H, Nizami S, Lee H, Stamer D, Patel N, Soung D, Back JH, Song L, Drissi H, Lee FY. Calreticulin inhibits inflammation‐induced osteoclastogenesis and bone resorption. Journal Of Orthopaedic Research® 2017, 35: 2658-2666. PMID: 28460421, PMCID: PMC8996436, DOI: 10.1002/jor.23587.Peer-Reviewed Original ResearchConceptsRecombinant human calreticulinIntracellular proteinsCalcium-binding chaperoneDifferent cell typesRecombinant formTranscription factorsFusion of monocytesExtracellular functionsNew therapeutic opportunitiesK activityCathepsin K activityCell typesCalreticulinCytoplasmic 1Anti-osteoclastogenic effectPrecursor cellsMetastatic bone cancerFactor 1Human calreticulinActivated T cellsOsteoclast precursor cellsProteinNuclear factorC-fosMouse calvarial bones
2015
Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential
Worthley DL, Churchill M, Compton JT, Tailor Y, Rao M, Si Y, Levin D, Schwartz MG, Uygur A, Hayakawa Y, Gross S, Renz BW, Setlik W, Martinez AN, Chen X, Nizami S, Lee HG, Kang HP, Caldwell JM, Asfaha S, Westphalen CB, Graham T, Jin G, Nagar K, Wang H, Kheirbek MA, Kolhe A, Carpenter J, Glaire M, Nair A, Renders S, Manieri N, Muthupalani S, Fox JG, Reichert M, Giraud AS, Schwabe RF, Pradere JP, Walton K, Prakash A, Gumucio D, Rustgi AK, Stappenbeck TS, Friedman RA, Gershon MD, Sims P, Grikscheit T, Lee FY, Karsenty G, Mukherjee S, Wang TC. Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential. Cell 2015, 160: 269-284. PMID: 25594183, PMCID: PMC4436082, DOI: 10.1016/j.cell.2014.11.042.Peer-Reviewed Original ResearchConceptsBone morphogenetic proteinStem cellsMarrow stromal cellsMesenchymal stem cellsGremlin-1Skeletal stem cellsTissue stem cellsFate-mapping experimentsStromal cellsMorphogenetic proteinsPostnatal skeletonBone developmentCell of originMesenchymal sheathCellsAdipocytesOsteoblastsExpressionBone marrowChondrocytesProteinBone remodelingPerisinusoidal spaceRemodelingFracture repair
2014
Effects of biomechanical forces on signaling in the cortical collecting duct (CCD)
Carrisoza-Gaytan R, Liu Y, Flores D, Else C, Lee HG, Rhodes G, Sandoval RM, Kleyman TR, Lee FY, Molitoris B, Satlin LM, Rohatgi R. Effects of biomechanical forces on signaling in the cortical collecting duct (CCD). American Journal Of Physiology. Renal Physiology 2014, 307: f195-f204. PMID: 24872319, PMCID: PMC4152160, DOI: 10.1152/ajprenal.00634.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutocrine CommunicationCell LineDinoprostoneEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFurosemideInjectionsIon TransportKidney CortexKidney Tubules, CollectingMechanotransduction, CellularMiceMicroscopy, Fluorescence, MultiphotonP38 Mitogen-Activated Protein KinasesParacrine CommunicationPhosphorylationPotassiumRatsRats, Sprague-DawleySodium ChlorideStress, MechanicalTime FactorsConceptsTubular fluid flow rateP-p38Biomechanical forcesCircumferential stretchIntravital microscopic approachP-ERK expressionFurosemide injectionPGE2 releaseIntracellular MAPKK secretionCollagen type IVCell culture modelTubular diameterEx vivoPGE2Fluid shear stressUnstretched controlsCCD cellsType IVP38 activationCulture modelMAPK signalingVivoPhysiological forcesCation transport
2012
Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells
Lee HG, Hsu A, Goto H, Nizami S, Lee JH, Cadet ER, Tang P, Shaji R, Chandhanayinyong C, Kweon SH, Oh DS, Tawfeek H, Lee FY. Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells. American Journal Of Physiology - Cell Physiology 2012, 304: c431-c439. PMID: 23255578, PMCID: PMC3602649, DOI: 10.1152/ajpcell.00202.2012.Peer-Reviewed Original ResearchConceptsBone-implant junctionEffect of particlesAbsence of TiWear particlesShear stressMechanical loadingTitanium particlesMetal implantsMechanical perturbationsMechanical strainFluid pressureParticlesBone tissueOsseous integrationTiOsteoprogenitor cellsImplant failureLoadingGene expressionCombined effectMechanical stimuliInterface
2011
New application of optical agent to image angiogenesis in hindlimb ischemia
Tekabe Y, Klose A, Nizami S, Luma J, Lee FY, Johnson L. New application of optical agent to image angiogenesis in hindlimb ischemia. Journal Of Biophotonics 2011, 4: 859-865. PMID: 22031282, DOI: 10.1002/jbio.201100038.Peer-Reviewed Original ResearchActin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells
Lee HG, Minematsu H, Kim KO, Aydemir A, Shin MJ, Nizami SA, Chung KJ, Hsu AC, Jacobs CR, Lee FY. Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells. Biomaterials 2011, 32: 9197-9206. PMID: 21899882, PMCID: PMC3193180, DOI: 10.1016/j.biomaterials.2011.08.059.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdhesivenessAnimalsBenzimidazolesBone and BonesCCAAT-Enhancer-Binding Protein-betaCyclooxygenase 2Cytochalasin DExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansImmunity, InnateInflammationInterleukin-6MAP Kinase Signaling SystemMiceModels, BiologicalOsteogenesisOsteolysisPhagocytosisProtein Kinase InhibitorsSignal TransductionSkullStem CellsTime FactorsTitaniumConceptsInflammatory osteolysisInflammatory responseMacrophage-mediated inflammatory responsesKey inflammatory pathwaysSuitable therapeutic targetInflammatory gene expressionInnate immune responseOsteoprogenitor cellsInflammatory cascadeInflammatory pathwaysImmune responseTherapeutic targetHost bone-implant interfaceAZD6244 treatmentIntracellular mechanismsBone-implant interfaceBone formationCellular mechanismsERK pathwayInflammationΒ pathwayOsteoclastogenesisOsteolysisIntracellular signalingImplant osteointegrationNuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages
Minematsu H, Shin MJ, Aydemir A, Kim KO, Nizami SA, Chung GJ, Lee FY. Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages. Cellular Signalling 2011, 23: 1785-1793. PMID: 21726630, PMCID: PMC3169434, DOI: 10.1016/j.cellsig.2011.06.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone MarrowCell NucleusChromatin ImmunoprecipitationCytokinesHumansImmunity, InnateImmunohistochemistryLipopeptidesLipopolysaccharidesMacrophagesMiceMice, KnockoutMonocytesNF-kappa BNFATC Transcription FactorsOligopeptidesPrimary Cell CultureRNA Polymerase IIRNA, MessengerSignal TransductionToll-Like ReceptorsTumor Necrosis Factor-alphaConceptsBone marrow-derived macrophagesInnate immune responseImmune responseLPS stimulationNuclear factorNFAT-luciferase reporterProinflammatory cytokine expressionInnate inflammatory responseTLR ligand stimulationToll-like receptorsActivated T cells c3Monocytes/macrophagesActivated T cellsInnate immune regulationRole of NFATsTNF mRNA expressionMarrow-derived macrophagesImmune regulatory proteinsTLR4 ligandCytokine expressionLess TNFTLR1/2 ligandInflammatory responseImmune regulationT cellsTargeting Inflammatory Kinase as an Adjuvant Treatment for Osteosarcomas
Noh K, Kim KO, Patel NR, Staples JR, Minematsu H, Nair K, Lee FY. Targeting Inflammatory Kinase as an Adjuvant Treatment for Osteosarcomas. Journal Of Bone And Joint Surgery 2011, 93: 723-732. PMID: 21508279, PMCID: PMC6882535, DOI: 10.2106/jbjs.j.00302.Peer-Reviewed Original ResearchConceptsOsteosarcoma-bearing miceDoxorubicin treatmentVehicle-treated control miceVehicle-treated miceSubset of patientsConventional cytotoxic chemotherapyCell deathOsteosarcoma cellsAnti-cancer effectsAnti-apoptotic protein expressionSignal-regulated kinase 1/2Bcl-2-mediated resistanceInflammatory kinasesAdjuvant treatmentCytotoxic chemotherapyUntreated miceControl miceTreatment outcomesTherapeutic effectERK pathway inhibitorAnti-apoptotic proteinsNude miceAnimal morbidityAggressive osteosarcomaOsteosarcoma cell death
2009
Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis
Seo SW, Lee D, Minematsu H, Kim AD, Shin M, Cho SK, Kim DW, Yang J, Lee FY. Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis. Bone 2009, 46: 695-702. PMID: 19895919, PMCID: PMC2823832, DOI: 10.1016/j.bone.2009.10.032.Peer-Reviewed Original ResearchConceptsInflammatory osteolysisInflammatory responseInnate immune responseExtracellular signal-regulated kinase (ERK) signalingImportant therapeutic targetM-CSF expressionSignal-regulated kinase 1/2 pathwaySignal-regulated kinase signalingExtracellular signal-regulated kinase 1/2 (ERK1/2) pathwayInhibition of ERKImmune responseTherapeutic implicationsTherapeutic targetOsteoclast precursorsKinase 1/2 pathwayM-CSFOsteolysisERK pathwayMacrophage colonyLPSERKERK signalsMitogen-activated protein kinase (MAPK) familyKinase signalingCell differentiationNuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced Cox2 in human and murine bone cells
Aydemir A, Minematsu H, Gardner TR, Kim KO, Ahn JM, Lee FY. Nuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced Cox2 in human and murine bone cells. Bone 2009, 46: 167-175. PMID: 19748606, PMCID: PMC2818272, DOI: 10.1016/j.bone.2009.08.061.Peer-Reviewed Original ResearchConceptsActivated T cellsT cellsBone cellsMechanical stimulationNuclear factorPathways of inflammationCytokine gene inductionMouse bone cellsMurine bone cellsBone massCOX2 inductionCOX2 expressionStability of implantsCalvarial bone cellsOsseous integrationHost boneNuclear translocationFluid shear stressDaily activitiesStimulationTranscription factorsNovel roleImplantsNFAT2Osteoblastic lineage