Featured Publications
TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity
Fu W, Hu W, Yi Y, Hettinghouse A, Sun G, Bi Y, He W, Zhang L, Gao G, Liu J, Toyo-oka K, Xiao G, Solit D, Loke P, Liu C. TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity. Journal Of Clinical Investigation 2021, 131 PMID: 34185706, PMCID: PMC8363273, DOI: 10.1172/jci144016.Peer-Reviewed Original ResearchConceptsMacrophage polarizationMacrophage plasticityPI3K/Akt/mTORPathogenesis of inflammationMyeloid-specific deletionNF-κB activationAkt/mTORInflammatory arthritisAntiinflammatory pathwayImmunoregulatory roleAutoimmune diseasesProtective effectTherapeutic implicationsInflammationTNFR2 signalingAutoimmunityTNFR2TNFR2 activationReceptor complexDiseaseIntracellular regulatorsActivationMolecule 14TNFR1Arthritis14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis
Fu W, Hettinghouse A, Chen Y, Hu W, Ding X, Chen M, Ding Y, Mundra J, Song W, Liu R, Yi Y, Attur M, Samuels J, Strauss E, Leucht P, Schwarzkopf R, Liu C. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Annals Of The Rheumatic Diseases 2021, 80: 1615-1627. PMID: 34226187, PMCID: PMC8595573, DOI: 10.1136/annrheumdis-2021-220000.Peer-Reviewed Original ResearchConceptsPathogenesis of osteoarthritisTNFR2 complexTherapeutic effectSingle-cell RNA-seqIntracellular componentsReceptor complexExtracellular signal-regulated kinaseNuclear factor kappa BSignal-regulated kinaseCommon joint diseaseFactor kappa BChondrocyte-specific deletionProteomic screenElk-1RNA-seqTranscription factorsCell-based assaysTNF signalingTNFR2 pathwayInducible componentJoint diseaseActivity screenTherapeutic targetKappa BOsteoarthritisFexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis
Liu R, Chen Y, Fu W, Wang S, Cui Y, Zhao X, Lei Z, Hettinghouse A, Liu J, Wang C, Zhang C, Bi Y, Xiao G, Chen Z, Liu C. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis. Annals Of The Rheumatic Diseases 2019, 78: 1524. PMID: 31302596, PMCID: PMC8157820, DOI: 10.1136/annrheumdis-2019-215543.Peer-Reviewed Original ResearchConceptsAnti-TNF activityCytosolic phospholipase A2Inflammatory arthritisTNF-α transgenic miceInflammatory arthritis modelInflammatory rheumatic diseasesCollagen-induced arthritisAnti-inflammatory activityPhospholipase A2New therapeutic interventionsActivated B cellsTNF-α signalingNecrosis factor-alpha signalingDrug affinity responsive target stabilityDBA/1 miceRheumatic diseasesArthritis modelAutoimmune diseasesCellular thermal shiftSerial screeningB cellsTransgenic miceArthritisDrug AdministrationTherapeutic interventionsProgranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling
Zhao Y, Liu B, Tian Q, Wei J, Richbourgh B, Liu C. Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling. Annals Of The Rheumatic Diseases 2014, 74: 2244. PMID: 25169730, PMCID: PMC4408266, DOI: 10.1136/annrheumdis-2014-205779.Peer-Reviewed Original ResearchConceptsPGRN-deficient miceProgression of OAOA modelTumor necrosis factor αMechanism of progranulinRecombinant PGRN proteinArthritis mouse modelOA-like phenotypeRole of progranulinNecrosis factor αPathogenesis of OAJoint degenerative diseaseTNF receptor 2Degradation of cartilageExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Β-catenin signalingInflammatory actionsOA progressionAnabolic biomarkersAnabolic effectsOA developmentSafranin O stainingTherapeutic roleMouse modelADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis
Lai Y, Bai X, Zhao Y, Tian Q, Liu B, Lin E, Chen Y, Lee B, Appleton C, Beier F, Yu X, Liu C. ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis. Annals Of The Rheumatic Diseases 2013, 73: 1575. PMID: 23928557, PMCID: PMC4418017, DOI: 10.1136/annrheumdis-2013-203561.Peer-Reviewed Original ResearchConceptsADAMTS-7ADAMTS-7 expressionRat OA modelPathogenesis of osteoarthritisNF-κB signalingOA modelOA progressionCartilage degradationOA-like phenotypeTumor necrosis factorProgression of osteoarthritisJoint degenerative diseaseDownstream NF-κB signalingPotential molecular targetsPositive feedback loopShort-limbed dwarfismDisease progressionOA developmentNecrosis factorSafranin O stainingYoung miceUpregulated TNFReporter gene assayOsteoarthritisTransgenic miceThe Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice. Science 2011, 332: 478-484. PMID: 21393509, PMCID: PMC3104397, DOI: 10.1126/science.1199214.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsAnti-Inflammatory Agents, Non-SteroidalArthritis, ExperimentalCartilage, ArticularFemaleGranulinsHumansIntercellular Signaling Peptides and ProteinsLigandsMaleMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMiddle AgedProgranulinsProtein Interaction Domains and MotifsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaYoung AdultConceptsInflammatory arthritisAdministration of progranulinAntagonist of TNFαCollagen-induced arthritisArthritis mouse modelPGRN-deficient miceNew potential therapeutic interventionsPotential therapeutic interventionsGrowth factor progranulinNecrosis factor receptorRheumatoid arthritisMouse modelArthritisTherapeutic interventionsProgranulinTNF receptorFactor receptorMiceReceptorsInflammationTissue repairTNFαIntracellular signalingAtsttrinTNFR
2024
Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases
Zhou R, Hu W, Ma P, Liu C. Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases. Bone Research 2024, 12: 58. PMID: 39406741, PMCID: PMC11480210, DOI: 10.1038/s41413-024-00370-4.Peer-Reviewed Original Research
2019
Progranulin promotes diabetic fracture healing in mice with type 1 diabetes
Wei J, Zhang L, Ding Y, Liu R, Guo Y, Hettinghouse A, Buza J, De La Croix J, Li X, Einhorn T, Liu C. Progranulin promotes diabetic fracture healing in mice with type 1 diabetes. Annals Of The New York Academy Of Sciences 2019, 1460: 43-56. PMID: 31423598, PMCID: PMC8138779, DOI: 10.1111/nyas.14208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondrogenesisDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Extracellular Signal-Regulated MAP KinasesFracture HealingGene DeletionHumansInflammationMiceProgranulinsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis FactorRecombinant ProteinsSignal TransductionTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaConceptsDiabetic fracture healingFracture healingTumor necrosis factor receptorProinflammatory cytokine tumor necrosisType 1 diabetes mellitusAnti-inflammatory signaling pathwaysCytokine tumor necrosisType 1 diabetesNovel therapeutic intervention strategiesGrowth factor-like moleculesTherapeutic intervention strategiesNecrosis factor receptorDiabetic fractureBone fracture healingDiabetes mellitusInsulin deficiencyAutoimmune diseasesTumor necrosisTherapeutic effectBone fracturesVivo modelDiabetesFactor receptorHealingIntervention strategies
2018
Targeting tumor necrosis factor receptors in ankylosing spondylitis
Lata M, Hettinghouse A, Liu C. Targeting tumor necrosis factor receptors in ankylosing spondylitis. Annals Of The New York Academy Of Sciences 2018, 1442: 5-16. PMID: 30008173, PMCID: PMC6333510, DOI: 10.1111/nyas.13933.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsHumansReceptors, Tumor Necrosis FactorSignal TransductionSpondylitis, AnkylosingTumor Necrosis Factor-alphaConceptsRole of TNFTumor necrosis factor inhibitorsCourse of ASTargeted biologic therapiesAnti-TNF therapyAutoimmune inflammatory disorderNecrosis factor inhibitorsMore effective treatment strategiesSerious adverse effectsMultiple clinical trialsEffective treatment strategiesPathogenesis of ASTumor necrosis factor receptorNecrosis factor receptorBiologic therapyTNF inhibitorsFactor inhibitorsInflammatory disordersPathogenic roleClinical trialsTreatment strategiesImmune pathwaysTNFTNF biologyTherapyp204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice
Yi Y, Jian J, Gonzalez-Gugel E, Shi Y, Tian Q, Fu W, Hettinghouse A, Song W, Liu R, He M, Qi H, Yang J, Du X, Xiao G, Chen L, Liu C. p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice. EBioMedicine 2018, 29: 78-91. PMID: 29472103, PMCID: PMC5925582, DOI: 10.1016/j.ebiom.2018.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesGenotypeImmunity, InnateInflammasomesInflammation MediatorsInterferon Regulatory Factor-3Interferon-betaLipopolysaccharidesMacrophage ActivationMacrophagesMiceMice, KnockoutModels, BiologicalNF-kappa BNuclear ProteinsPhosphoproteinsProtein BindingProtein MultimerizationRAW 264.7 CellsShock, SepticSignal TransductionToll-Like Receptor 4ConceptsPro-inflammatory cytokinesLPS challengeIRF-3 pathwayDimerization of TLR4Serum levelsLPS-TLR4TLR4 signalingNF-ĸBAnimal modelsPyrin domainInnate immunityExtracellular LPSInterferon-inducible p200 familyInfectious diseasesLPSMicePotential targetTLR4IFNCytokinesMacrophagesBacterial DNASignificant defectsDramatic reductionPathway
2016
Review: Novel Insights Into Tumor Necrosis Factor Receptor, Death Receptor 3, and Progranulin Pathways in Arthritis and Bone Remodeling
Williams A, Wang E, Thurner L, Liu C. Review: Novel Insights Into Tumor Necrosis Factor Receptor, Death Receptor 3, and Progranulin Pathways in Arthritis and Bone Remodeling. Arthritis & Rheumatology 2016, 68: 2845-2856. PMID: 27428882, PMCID: PMC5599977, DOI: 10.1002/art.39816.Peer-Reviewed Original Research
2014
Progranulin inhibition of TNFα
Uddin S, Mundra J, Jian J, Tian Q, Gonzalez‐Gugel E, Richbourgh B, Liu C. Progranulin inhibition of TNFα. Immunology And Cell Biology 2014, 92: 299-300. PMID: 24518982, DOI: 10.1038/icb.2014.7.Peer-Reviewed Original Research
2013
The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling
Zhao Y, Tian Q, Frenkel S, Liu C. The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 2013, 34: 6412-6421. PMID: 23746860, PMCID: PMC3713419, DOI: 10.1016/j.biomaterials.2013.05.030.Peer-Reviewed Original ResearchConceptsBone healing processBone formationHealing processEctopic bone formationTNF-α transgenic miceBone healingTNFR2-deficient miceRole of PGRNTreatment of fracturesTNF-α signalingEndochondral ossificationPotential molecular targetsEctopic bone formation modelInflammatory osteoclastogenesisTNF/TNFRPGRN deficiencyInflammatory conditionsDeficient miceRecombinant PGRNBone regenerationTransgenic micePGRNMiceCritical mediatorGrowth factorProgranulin deficiency exaggerates, whereas progranulin‐derived Atsttrin attenuates, severity of dermatitis in mice
Zhao Y, Tian Q, Liu C. Progranulin deficiency exaggerates, whereas progranulin‐derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Letters 2013, 587: 1805-1810. PMID: 23669357, PMCID: PMC3683372, DOI: 10.1016/j.febslet.2013.04.037.Peer-Reviewed Original ResearchConceptsInflammatory skin diseaseSeverity of dermatitisMouse dermatitis modelNF-κB signalingPotential molecular targetsInflammatory arthritisDermatitis modelSkin inflammationPGRN levelsSevere inflammationProgranulin deficiencySkin diseasesProtective roleInflammationMolecular targetsPGRNAtsttrinDermatitisOxazoloneArthritisTNFαProgranulinDiseaseMiceProtein
2010
Granulin epithelin precursor: a bone morphogenic protein 2‐inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis
Feng J, Guo F, Jiang B, Zhang Y, Frenkel S, Wang D, Tang W, Xie Y, Liu C. Granulin epithelin precursor: a bone morphogenic protein 2‐inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. The FASEB Journal 2010, 24: 1879-1892. PMID: 20124436, PMCID: PMC2874481, DOI: 10.1096/fj.09-144659.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBlotting, WesternBone Morphogenetic Protein 2CartilageCell DifferentiationCells, CulturedChondrocytesChondrogenesisChromatin ImmunoprecipitationFetusGene Expression ProfilingHumansImmunoenzyme TechniquesIn Situ HybridizationIntercellular Signaling Peptides and ProteinsMesenchymal Stem CellsMiceMice, Inbred C3HMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oligonucleotide Array Sequence AnalysisProgranulinsProto-Oncogene Proteins c-junRabbitsReverse Transcriptase Polymerase Chain ReactionRNA ProbesRNA, MessengerSignal TransductionConceptsJunB transcription factorKey downstream moleculeGranulin-epithelin precursorChondrocyte differentiationTranscription factorsDownstream moleculesNovel critical roleGrowth factorBone morphogenic proteinBone morphogenic protein-2Molecular eventsMesenchymal stem cellsERK1/2 signalingProtein 2Morphogenic proteinStem cellsDifferentiationBMP2Critical roleTissue regenerationVivoSignalingCartilage repairProteinChondrogenesis
2008
Regulation of chondrocyte differentiation by ADAMTS-12 metalloproteinase depends on its enzymatic activity
Bai X, Wang D, Luan Y, Yu X, Liu C. Regulation of chondrocyte differentiation by ADAMTS-12 metalloproteinase depends on its enzymatic activity. Cellular And Molecular Life Sciences 2008, 66: 667. PMID: 19151918, PMCID: PMC11131527, DOI: 10.1007/s00018-008-8633-x.Peer-Reviewed Original ResearchConceptsADAMTS-12Chondrocyte differentiationGrowth plate chondrocytesType X collagen expressionThrombospondin motifsPTHrPCollagen expressionAltered expressionMRNA levelsProminent expressionDownstream moleculesADAMTS familyMetalloproteinaseInhibitionEnzymatic activityNovel regulatorProteolytic activityChondrocytesExpressionChondrogenesisDifferentiationActivityCbfa1-dependent expression of an interferon-inducible p204 protein is required for chondrocyte differentiation
Zhang Y, Kong L, Carlson C, Liu C. Cbfa1-dependent expression of an interferon-inducible p204 protein is required for chondrocyte differentiation. Cell Death & Differentiation 2008, 15: 1760-1771. PMID: 18636074, DOI: 10.1038/cdd.2008.112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBone Morphogenetic Protein 2Cell DifferentiationChondrocytesChondrogenesisCollagen Type XCore Binding Factor Alpha 1 SubunitEmbryo, MammalianGrowth PlateHedgehog ProteinsHypertrophyImmunohistochemistryMiceModels, BiologicalMolecular Sequence DataNuclear ProteinsParathyroid Hormone-Related ProteinPhosphoproteinsPromoter Regions, GeneticProtein BindingRNA, Small InterferingSignal TransductionSOXD Transcription FactorsTranscriptional ActivationConceptsChondrocyte hypertrophyChondrocyte differentiationMatrix metalloproteinase-13Indian hedgehogHypertrophic chondrocyte differentiationGrowth plate chondrocytesMetalloproteinase-13P204 proteinReceptor 1HypertrophyAltered levelsType X collagenAltered expressionEnhanced expressionProminent expressionSiRNA approachOverexpression of p204Collagen XSpecific reporter genesPluripotent C3H10T1/2 cellsX collagenNovel regulatorExpressionCbfa1C3H10T1/2 cells