Featured Publications
Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease
Jian J, Tian Q, Hettinghouse A, Zhao S, Liu H, Wei J, Grunig G, Zhang W, Setchell K, Sun Y, Overkleeft H, Chan G, Liu C. Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease. EBioMedicine 2016, 13: 212-224. PMID: 27789271, PMCID: PMC5264254, DOI: 10.1016/j.ebiom.2016.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalFibroblastsGaucher DiseaseGlucosylceramidaseHSP70 Heat-Shock ProteinsHumansIntercellular Signaling Peptides and ProteinsLysosome-Associated Membrane GlycoproteinsLysosomesMiceMice, KnockoutPhenotypeProgranulinsProtein AggregatesProtein BindingRecombinant ProteinsStress, PhysiologicalConceptsGaucher diseaseLysosomal storage diseaseStorage diseaseCommon lysosomal storage diseaseNew therapeutic interventionsΒ-glucocerebrosidaseProgranulin insufficiencyAnimal modelsTherapeutic interventionsDiseasePGRNDisease phenotypePatient fibroblastsGCaseComplex-associated proteinsLysosomal localizationHSP70Deficiency
2024
Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity
Sahu D, Gupta C, Yennamalli R, Sharma S, Roy S, Hasan S, Gupta P, Sharma V, Kashyap S, Kumar S, Dwivedi V, Zhao X, Panda A, Das H, Liu C. Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity. Scientific Reports 2024, 14: 12935. PMID: 38839973, PMCID: PMC11153517, DOI: 10.1038/s41598-024-63790-6.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsGel mobility-shift assaysCollagen-induced arthritisMobility-shift assaysCell surface receptorsFluorescence-activated cell sortingSequence strandsBinding of TNFIn silico methodsCell deathMouse modelSurface receptorsNuclear translocationTrimer formationCell culture assaysRheumatoid arthritisVicious cycle of inflammationModel of collagen-induced arthritisTumor necrosis factor-aCell sortingMouse model of collagen-induced arthritisA549 cellsCycle of inflammationInflammatory bone destructionCulture assay
2020
In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity
Fu W, Hettinghouse A, Liu C. In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity. Methods In Molecular Biology 2020, 2248: 109-119. PMID: 33185871, PMCID: PMC8112733, DOI: 10.1007/978-1-0716-1130-2_8.Peer-Reviewed Original ResearchConceptsAnti-TNFα activityAutoimmune diseasesTartrate-resistant acid phosphatase (TRAP) stainingAnti-TNFα therapyCollagen-induced arthritisInflammatory disease modelsGood therapeutic effectAcid phosphatase stainingGrowth factor-like moleculesTNF inhibitorsTherapeutic effectTNFα activityProgranulinFunctional inhibitionTNFR2AtsttrinDisease modelsPhosphatase stainingTNFRTNFαDiseaseInhibitionCritical roleDirect bindingHigh affinity
2018
p204 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
2011
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
Du Y, Wang Y, Wang L, Liu B, Tian Q, Liu C, Zhang T, Xu Q, Zhu Y, Ake O, Qi Y, Tang C, Kong W, Wang X. Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2. Circulation Research 2011, 108: 917-928. PMID: 21350216, DOI: 10.1161/circresaha.110.234328.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsCartilage oligomeric matrix proteinVascular calcificationOligomeric matrix proteinVSMC calcificationVascular smooth muscle calcificationMarker expressionHigh-phosphate dietSmooth muscle cellsCOMP deficiencyMuscle calcificationCardiovascular morbidityOsteogenic marker expressionAbdominal aortaVessel calcificationHigh inorganic phosphateEffects of COMPPeriadventitial applicationMatrix proteinsMuscle cellsCalcificationBMP-2Receptor bindingProtein levelsOsteogenic signaling
2010
Interaction between cartilage oligomeric matrix protein and extracellular matrix protein 1 mediates endochondral bone growth
Kong L, Tian Q, Guo F, Mucignat M, Perris R, Sercu S, Merregaert J, Di Cesare P, Liu C. Interaction between cartilage oligomeric matrix protein and extracellular matrix protein 1 mediates endochondral bone growth. Matrix Biology 2010, 29: 276-286. PMID: 20138147, PMCID: PMC2862898, DOI: 10.1016/j.matbio.2010.01.007.Peer-Reviewed Original ResearchConceptsExtracellular matrix protein 1Matrix protein 1EGF domainsFunctional genetic screensProtein 1Endochondral bone growthGenetic screenEndochondral bone formationBiological functionsC-terminusMatrix proteinsMatrix mineralizationBiological significanceCartilage oligomeric matrix proteinOligomeric matrix proteinChondrocyte hypertrophyFirst evidenceBone growthInhibitionGrowthColocalizeBone formationDomainProteinInteraction
2009
ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor
Bai X, Wang D, Kong L, Zhang Y, Luan Y, Kobayashi T, Kronenberg H, Yu X, Liu C. ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor. Molecular And Cellular Biology 2009, 29: 4201-4219. PMID: 19487464, PMCID: PMC2715794, DOI: 10.1128/mcb.00056-09.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS7 ProteinAnimalsBlotting, WesternBone and BonesBone DevelopmentCell DifferentiationCell LineCell Line, TumorChondrocytesGene Expression ProfilingHumansImmunohistochemistryImmunoprecipitationIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutParathyroid Hormone-Related ProteinProgranulinsProtein BindingProtein PrecursorsReverse Transcriptase Polymerase Chain ReactionTissue Culture TechniquesTwo-Hybrid System TechniquesConceptsADAMTS-7Granulin-epithelin precursorEndochondral bone formationEndochondral bone growthGrowth factorBone formationChondrocyte differentiationBone growthDirect targetAutocrine growth factorGrowth plate chondrocytesProteolytic activityPTHrPChondrogenic growth factorsChondrocyte hypertrophyExtracellular matrix proteinsCartilage extracellular matrix proteinsImportant targetADAMTS familyInhibitionSkeletal developmentMatrix proteinsExpression patternsExtracellular matrixArthritis
2008
Cbfa1-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 cellsp204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins
Luan Y, Yu X, Yang N, Frenkel S, Chen L, Liu C. p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins. Molecular Biology Of The Cell 2008, 19: 2113-2126. PMID: 18287524, PMCID: PMC2366862, DOI: 10.1091/mbc.e07-10-1057.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAmino Acid SequenceAnimalsBone Morphogenetic Protein 2Bone Morphogenetic ProteinsCell DifferentiationCell LineCell NucleusCore Binding Factor alpha SubunitsFemaleHelix-Loop-Helix MotifsHumansInhibitor of Differentiation ProteinsMiceMice, Inbred BALB CNuclear Export SignalsNuclear ProteinsOsteoblastsOsteocalcinOsteogenesisPhosphoproteinsPromoter Regions, GeneticProteasome Endopeptidase ComplexProtein BindingProtein TransportTransforming Growth Factor betaUbiquitinConceptsD proteinsOsteogenic differentiationSequence-specific bindingUbiquitin-proteasome pathwayCore binding factor αExpression of Cbfa1Factor alpha 1P204 proteinExport signalHelix proteinsHelix-LoopRegulatory circuitsTarget genesInterferon-inducible proteinOsteocalcin geneMolecular mechanismsALP activityOsteoblast differentiationDiminished transcriptionCytoplasmic translocationId2Cbfa1Differentiation proteinProteinAlkaline phosphatase
2007
Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation*
Xu K, Zhang Y, Ilalov K, Carlson C, Feng J, Di Cesare P, Liu C. Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation*. Journal Of Biological Chemistry 2007, 282: 11347-11355. PMID: 17307734, DOI: 10.1074/jbc.m608744200.Peer-Reviewed Original ResearchConceptsGranulin-epithelin precursorCartilage oligomeric matrix proteinMutant cartilage oligomeric matrix proteinTwo-hybrid systemCo-immunoprecipitation assaysFunctional genetic screensChondrocyte proliferationHuman cartilage oligomeric matrix proteinGenetic screenRat chondrosarcoma cellsProtein associatesGrowth factorRepeat domainBiological functionsFunctional domainsMouse embryosMatrix proteinsAnti-COMP antibodiesChondrosarcoma cellsOligomeric matrix proteinAutocrine growth factorMultiple epiphyseal dysplasiaPericellular matrixPrimary human chondrocytesRepeat units
2006
ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein*
Liu C, Kong W, Xu K, Luan Y, Ilalov K, Sehgal B, Yu S, Howell R, Di Cesare P. ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein*. Journal Of Biological Chemistry 2006, 281: 15800-15808. PMID: 16611630, PMCID: PMC1483932, DOI: 10.1074/jbc.m513433200.Peer-Reviewed Original ResearchConceptsCartilage oligomeric matrix proteinADAMTS-12Matrix proteinsOligomeric matrix proteinCOMP degradationNoncollagenous matrix componentsSynovium of patientsProgression of arthritisEpidermal growth factor-like repeat domainRepeat domainExtracellular matrix breakdownFunctional domainsArticular cartilageMolecular mechanismsArthritis patientsRheumatoid arthritisSynovial fluidMatrix breakdownArthritisMatrix componentsDegradative fragmentsPatientsSynoviumProteinNormal cartilageADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein
Liu C, Kong W, Ilalov K, Yu S, Xu K, Prazak L, Fajardo M, Sehgal B, Di Cesare P, Liu C, Kong W, Ilalov K, Yu S, Xu K, Prazak L, Fajardo M, Sehgal B, Di Cesare P. ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. The FASEB Journal 2006, 20: 988-990. PMID: 16585064, PMCID: PMC1483927, DOI: 10.1096/fj.05-3877fje.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS7 ProteinAdultAgedAnimalsArthritis, RheumatoidBinding SitesCartilageCartilage Oligomeric Matrix ProteinExtracellular Matrix ProteinsGene Expression Regulation, EnzymologicGlycoproteinsHumansHydrogen-Ion ConcentrationMatrilin ProteinsMiceMiddle AgedProtein BindingRatsRNA, MessengerSynovial MembraneTwo-Hybrid System TechniquesUp-RegulationZincConceptsCartilage oligomeric matrix proteinMatrix proteinsEpidermal growth factor domainTwo-hybrid screenOligomeric matrix proteinGrowth factor domainRecombinant catalytic domainCatalytic domainRepeat domainFunctional domainsInteraction partnersADAMTS-7Factor domainAmino acidsEnzymatic activityProteinHigh expression