Featured Publications
Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis
Wang K, Ding X, Jiang N, Zeng C, Wu J, Cai X, Hettinghouse A, Khleborodova A, Lei Z, Chen Z, Lei G, Liu C. Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis. Annals Of The Rheumatic Diseases 2021, 81: 544-555. PMID: 34853001, PMCID: PMC9082564, DOI: 10.1136/annrheumdis-2021-221380.Peer-Reviewed Original ResearchConceptsLow-density lipoprotein receptor-related protein 4Lipoprotein receptor-related protein 4Digoxin useCohort studyChondroprotective actionChondrocyte anabolismHealth Improvement NetworkProtein 4Risk of osteoarthritisPathogenesis of osteoarthritisBinding of digoxinAtrial fibrillationChondroprotective effectsJoint osteoarthritisTherapeutic effectSerial screeningOA modelImprovement NetworkOsteoarthritisDrug AdministrationChondrocyte catabolismDigoxinJoint replacementNovel targetPotential stimulator14-3-3 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 BOsteoarthritisADAMTS-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 mice
2017
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
Wei J, Fu W, Ding Y, Hettinghouse A, Lendhey M, Schwarzkopf R, Kennedy O, Liu C. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models. Arthritis Research & Therapy 2017, 19: 280. PMID: 29258611, PMCID: PMC5735869, DOI: 10.1186/s13075-017-1485-8.Peer-Reviewed Original ResearchConceptsTherapeutic effectOA modelPain-related markersAnti-catabolic effectsRole of progranulinDegenerative joint diseaseMurine OA modelMultiple murine modelsNew therapeutic alternativesTumor necrosis factor receptorIntra-articular deliveryNecrosis factor receptorInflammatory arthritisPGRN deficiencyOA phenotypeSafranin O stainingTherapeutic alternativeRat modelJoint diseaseOsteoarthritis progressionPreventative effectMurine modelCartilage degradationDegenerative factorsEarly osteoarthritis
2016
Chondro-protective effects of low intensity pulsed ultrasound
Uddin S, Richbourgh B, Ding Y, Hettinghouse A, Komatsu D, Qin Y, Liu C. Chondro-protective effects of low intensity pulsed ultrasound. Osteoarthritis And Cartilage 2016, 24: 1989-1998. PMID: 27364595, PMCID: PMC5071131, DOI: 10.1016/j.joca.2016.06.014.Peer-Reviewed Original ResearchMeSH KeywordsCartilage, ArticularCells, CulturedChondrocytesHumansInterleukin-1betaOsteoarthritisUltrasonic WavesConceptsIL-1βHuman cartilage explantsCartilage degradationMesenchymal stem cellsIL-1β induced activationPotential therapeutic effectsChondro-protective effectsPathogenesis of osteoarthritisLIPUS stimulationCartilage explantsChondrocyte migrationWestern blot analysisLoss of proteoglycanTherapeutic effectNFκB p65Catabolic actionMetabolic alterationsNFκB pathwayOsteoarthritisReduced expressionChondrocyte metabolismInduced activationMechanical stimulationLIPUSStimulation
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 formationDomainProteinInteractionGranulin 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
2009
The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey
Lengyel P, Liu CJ. The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey. Cellular And Molecular Life Sciences 2009, 67: 335-340. PMID: 19921484, PMCID: PMC2824682, DOI: 10.1007/s00018-009-0195-z.Peer-Reviewed Original ResearchConceptsTranscription factorsTissue-specific transcription factorsParticular transcription factorsRibosomal RNA synthesisCell proliferationSkeletal muscle myotubesUnexplored tissuesMuscle myotubesCell cyclingDifferentiation proteinRNA synthesisNumerous tissuesP204DifferentiationProteinCardiac myocytesProliferationTissueMyotubesCytoplasmNucleoliOsteoblastsExpressionActivityRAADAMTS-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 matrixArthritismiR-199a*, a Bone Morphogenic Protein 2-responsive MicroRNA, Regulates Chondrogenesis via Direct Targeting to Smad1*
Lin E, Kong L, Bai X, Luan Y, Liu C. miR-199a*, a Bone Morphogenic Protein 2-responsive MicroRNA, Regulates Chondrogenesis via Direct Targeting to Smad1*. Journal Of Biological Chemistry 2009, 284: 11326-11335. PMID: 19251704, PMCID: PMC2670138, DOI: 10.1074/jbc.m807709200.Peer-Reviewed Original Research
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 activityChondrocytesExpressionChondrogenesisDifferentiationActivityMediation of Chondrogenic and Osteogenic Differentiation by an Interferon-Inducible p202 Protein
Kong L, Liu C. Mediation of Chondrogenic and Osteogenic Differentiation by an Interferon-Inducible p202 Protein. Cellular And Molecular Life Sciences 2008, 65: 3494-3506. PMID: 18791844, PMCID: PMC11131663, DOI: 10.1007/s00018-008-8342-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineChondrocytesChondrogenesisFeedback, PhysiologicalGene Expression Regulation, DevelopmentalGene Knockdown TechniquesGenes, ReporterGrowth PlateIntracellular Signaling Peptides and ProteinsMiceMice, Inbred C3HMice, KnockoutMice, TransgenicOsteoblastsOsteogenesisParathyroid Hormone-Related ProteinPluripotent Stem CellsRNA, Small InterferingSmad ProteinsConceptsParathyroid hormone-related peptideExpression of PTHrPHormone-related peptideCourse of osteogenesisGrowth plate chondrocytesInterferon-inducible proteinMolecular mechanism studiesInterferon-inducible p200 familyImportant mediatorP202 proteinOsteogenic differentiationSiRNA approachMouse embryosP202 expressionChondrocyte differentiationPositive feedback loopSmad transcription factorsTransgenic mouse embryosOsteoblast differentiationDifferential expressionExpressionC3H10T1/2 cellsC2C12 cellsDifferentiationCellsCbfa1-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
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