2015
CA‐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 ResearchMeSH KeywordsAnimalsCathepsin BDipeptidesMaleMAP Kinase Signaling SystemMice, Inbred C57BLNFATC Transcription FactorsNF-kappa BOsteoclastsProto-Oncogene Proteins c-fosRANK LigandConceptsOsteolytic 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 inhibitsHarnessing endogenous stem/progenitor cells for tendon regeneration
Lee CH, Lee FY, Tarafder S, Kao K, Jun Y, Yang G, Mao JJ. Harnessing endogenous stem/progenitor cells for tendon regeneration. Journal Of Clinical Investigation 2015, 125: 2690-2701. PMID: 26053662, PMCID: PMC4563693, DOI: 10.1172/jci81589.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsCD146 AntigenCell DifferentiationCell ProliferationColony-Forming Units AssayConnective Tissue Growth FactorFocal Adhesion Kinase 1MAP Kinase Signaling SystemMultipotent Stem CellsRatsRats, Sprague-DawleyRegenerationTendon InjuriesTendonsTissue EngineeringWound HealingConceptsStem/progenitor cellsEndogenous stem/progenitor cellsProgenitor cellsCell transplantationTendon regenerationStem cell markers CD146Stem cell-based strategiesFAK/ERK1/2Cell-based strategiesRat modelTendon healingFunctional restorationNormal levelsMultilineage differentiation abilityClonogenic capacityCD146Tendon cellsSiRNA knockdownTransplantationVivo manipulation
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
Actin 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 osteointegration
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