Featured Publications
Enhancement 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 culturesBiocompatibility 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 cellsStrengthLocally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection
Cahill SV, Kwon H, Back J, Lee I, Lee S, Alder KD, Hao Z, Yu KE, Dussik CM, Kyriakides T, Lee F. Locally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection. Journal Of Orthopaedic Research® 2021, 39: 402-414. PMID: 33336805, DOI: 10.1002/jor.24965.Peer-Reviewed Original ResearchConceptsHigh-dose rifampinFracture healingMRSA infectionMethicillin-resistant Staphylococcus aureus osteomyelitisColony-forming unitsTissue bacterial loadStaphylococcus aureus osteomyelitisReactive bone formationRadiographic union scaleEndochondral fracture healingBacterial CFU countsPoor callus formationSoft callus formationTibia scoresRifampin therapyDevastating complicationMRSA colonizationClinical efficacyInfected fracturesTibial radiographsTreatment responseMurine modelIntramedullary pinOpen fracturesO stainSmoking 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 ResearchMeSH KeywordsAnimalsFracture HealingInflammationMiceMice, Inbred C57BLSmokingStem CellsX-Ray MicrotomographyConceptsCigarette 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
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
Dried plum alleviates symptoms of inflammatory arthritis in TNF transgenic mice
Mirza F, Lorenzo J, Drissi H, Lee FY, Soung DY. Dried plum alleviates symptoms of inflammatory arthritis in TNF transgenic mice. The Journal Of Nutritional Biochemistry 2017, 52: 54-61. PMID: 29149648, DOI: 10.1016/j.jnutbio.2017.10.002.Peer-Reviewed Original ResearchConceptsTumor necrosis factorTransgenic miceRheumatoid arthritisNuclear factor-kappa B activationDP dietBone-preserving propertiesReduction of synovitisPresence of TNFFour-week treatmentOnset of arthritisResistant acid phosphatase-positive cellsAcid phosphatase-positive cellsDestruction of jointsHuman synovial fibroblastsTNF-transgenic miceHuman tumor necrosis factorKappa B activationActivated T cellsFormation of osteoclastsMouse bone marrow macrophagesBone marrow macrophagesArticular cartilagePostmenopausal womenInflammatory arthritisBone erosionCalreticulin 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
Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response
Tascau L, Gardner T, Anan H, Yongpravat C, Cardozo CP, Bauman WA, Lee FY, Oh DS, Tawfeek HA. Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response. Endocrinology 2015, 157: 112-126. PMID: 26488807, DOI: 10.1210/en.2015-1614.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBone DensityCells, CulturedEnergy MetabolismEnzyme ActivationFemaleFemurLumbar VertebraeMaleMice, Inbred C57BLMice, TransgenicOsteoblastsOsteocytesOsteogenesisPoint MutationPromoter Regions, GeneticSex CharacteristicsUp-RegulationX-Ray MicrotomographyConceptsBone anabolic responseOb miceMature osteoblastsPKA activationHigher basal PKA activityControl miceAnabolic responseProtein kinase ASerum bone turnover markersBone volume/total volumeBone turnover markersBasal PKA activityFemur cortical thicknessTotal tissue areaActive PKAKinase AConstitutive activationPKA activityTurnover markersBone lossAnabolic drugsStructure model indexOsteoclast numberFemale miceBone massCA‐074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐FOS signaling pathways
Patel N, Nizami S, Song L, Mikami M, Hsu A, Hickernell T, Chandhanayingyong C, Rho S, Compton JT, Caldwell J, Kaiser PB, Bai H, Lee HG, Fischer CR, Lee FY. CA‐074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐FOS signaling pathways. Journal Of Orthopaedic Research® 2015, 33: 1474-1486. PMID: 25428830, DOI: 10.1002/jor.22795.Peer-Reviewed Original ResearchConceptsOsteolytic disordersOsteoclast biologyBone resorptionCA-074MeC-FOSMechanisms of cathepsinsCathepsin B knockout miceB knockout miceCathepsin B inhibitor CA-074Dose-dependent mannerOsteoclast resorption pitsCathepsin B inhibitionInhibits osteoclastogenesisNFATc1 pathwayNew therapiesOsteoclastogenic effectsCA-074Knockout miceLysosomal proteasesMature osteoclastsResorption pitsCathepsin KNew targetsOsteoclastsCompound inhibitsGremlin 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 ResearchMeSH KeywordsAnimalsBone and BonesCartilageIntercellular Signaling Peptides and ProteinsIntestine, SmallMesenchymal Stem CellsMiceMice, Inbred C57BLConceptsBone 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
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
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 differentiation
2007
Orthopedic Implant Particle‐Induced Tumor Necrosis Factor‐α Production in Macrophage–Monocyte Lineage Cells Is Mediated by Nuclear Factor of Activated T Cells
MINEMATSU H, SHIN MJ, AYDEMIR A, SEO SW, KIM DW, BLAINE TA, MACIÁN F, YANG J, LEE F. Orthopedic Implant Particle‐Induced Tumor Necrosis Factor‐α Production in Macrophage–Monocyte Lineage Cells Is Mediated by Nuclear Factor of Activated T Cells. Annals Of The New York Academy Of Sciences 2007, 1117: 143-150. PMID: 18056040, DOI: 10.1196/annals.1402.026.Peer-Reviewed Original ResearchConceptsActivated T cellsT cellsLineage cellsTumor Necrosis Factor-α ProductionNuclear factorMonocyte-macrophage lineage cellsTNF-alpha protein secretionTNF-alpha expressionTNF-alpha productionTNF-alpha gene expressionTumor necrosis factorMurine macrophage-like RAW264.7Macrophage-like RAW264.7TNF-alpha inductionMonocyte-macrophage cellsTNF-alphaNecrosis factorSpecific molecular mechanismsImplant particlesJoint prosthesesMolecular mechanisms