2014
Activation of β-catenin signalling leads to temporomandibular joint defects
Wang M, Li S, Xie W, Shen J, Im H, Holz J, Wang M, Diekwisch T, Chen D. Activation of β-catenin signalling leads to temporomandibular joint defects. ECells & Materials 2014, 28: 223-235. PMID: 25340802, PMCID: PMC4288590, DOI: 10.22203/ecm.v028a15.Peer-Reviewed Original ResearchConceptsDouble mutant miceTMJ disordersΒ-cateninMutant miceADAMTS5-/- miceRole of MMP13OA-like phenotypeTemporomandibular joint disordersMG reporter micePotential therapeutic targetDevelopment of TMJTMJ cartilage degenerationHip osteoarthritisTMJ samplesJoint disordersTherapeutic targetReporter miceTransgenic miceCartilage degenerationMiceTMJ cartilageADAMTS5 geneTMJADAMTS5MMP13
2013
Deletion of the Transforming Growth Factor β Receptor Type II Gene in Articular Chondrocytes Leads to a Progressive Osteoarthritis‐like Phenotype in Mice
Shen J, Li J, Wang B, Jin H, Wang M, Zhang Y, Yang Y, Im H, O'Keefe R, Chen D. Deletion of the Transforming Growth Factor β Receptor Type II Gene in Articular Chondrocytes Leads to a Progressive Osteoarthritis‐like Phenotype in Mice. Arthritis & Rheumatism 2013, 65: 3107-3119. PMID: 23982761, PMCID: PMC3928444, DOI: 10.1002/art.38122.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS5 ProteinAnimalsCartilage, ArticularChondrocytesCore Binding Factor Alpha 2 SubunitDisease ProgressionMatrix Metalloproteinase 13MiceMice, KnockoutOsteoarthritisPhenotypeProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionUp-RegulationConceptsCritical downstream target genesDownstream target genesTarget genesGrowth factor β signalingRegulation of Runx2Mouse genetic approachesLoss of TGFβType II geneGene expression analysisInhibition of TGFβDevelopment of osteoarthritisRat chondrosarcoma cellsGenetic approachesExpression analysisConditional knockout miceTGFβ signalingOsteoarthritis-like phenotypeGenesΒ signalingADAMTS5 geneReceptor type IIChondrosarcoma cellsTGFβCartilage homeostasisOA-like phenotype
2012
Conditional activation of β‐catenin signaling in mice leads to severe defects in intervertebral disc tissue
Wang M, Tang D, Shu B, Wang B, Jin H, Hao S, Dresser KA, Shen J, Im H, Sampson ER, Rubery PT, Zuscik MJ, Schwarz EM, O'Keefe RJ, Wang Y, Chen D. Conditional activation of β‐catenin signaling in mice leads to severe defects in intervertebral disc tissue. Arthritis & Rheumatism 2012, 64: 2611-2623. PMID: 22422036, PMCID: PMC3632450, DOI: 10.1002/art.34469.Peer-Reviewed Original ResearchConceptsDisc degenerationΒ-cateninDisc tissueExtensive osteophyte formationLow back painDisc tissue samplesIntervertebral disc degenerationPolymerase chain reaction assaysTissue functionBack painReal-time polymerase chain reaction assaysRunt-related transcription factorΒ-catenin protein levelsChain reaction assaysIntervertebral disc tissueOsteophyte formationΒ-catenin levelsImmunohistochemical analysisNormal subjectsMatrix metalloproteinase-13 inhibitorsTransgenic miceHistologic analysisΒ-catenin proteinADAMTS5 expressionGenetic ablationLead induces an osteoarthritis‐like phenotype in articular chondrocytes through disruption of TGF‐β signaling
Holz JD, Beier E, Sheu T, Ubayawardena R, Wang M, Sampson ER, Rosier RN, Zuscik M, Puzas JE. Lead induces an osteoarthritis‐like phenotype in articular chondrocytes through disruption of TGF‐β signaling. Journal Of Orthopaedic Research® 2012, 30: 1760-1766. PMID: 22517267, PMCID: PMC3839422, DOI: 10.1002/jor.22117.Peer-Reviewed Original ResearchConceptsLead treatmentOsteoarthritis-like phenotypeNormal chondrocyte phenotypeDose-dependent mannerArticular chondrocytesTGF-β signalingActive caspase-3MMP13 activityLead exposureHigher level leadType II collagenVivo exposureCollagen levelsNovel targetType X collagenCaspase-3Articular surfaceEnvironmental toxinsLead toxicityII collagenReporter activityTreatmentArticular cartilageDosePhenotypic shift
2011
Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis
Wang M, Shen J, Jin H, Im H, Sandy J, Chen D. Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis. Annals Of The New York Academy Of Sciences 2011, 1240: 61-69. PMID: 22172041, PMCID: PMC3671949, DOI: 10.1111/j.1749-6632.2011.06258.x.Peer-Reviewed Original ResearchConceptsMolecular mechanismsEffective disease-modifying treatmentDisease-modifying treatmentsIndian hedgehogCell typesMolecular levelExtracellular matrixΒ-cateninMutant miceOA patientsJoint injuryRecent findingsOA developmentHIF-2aTGF-β1Biomechanical alterationsOA subtypesCartilage degenerationPrevalent diseaseOsteoarthritisPathwayVivo studiesReceptor ligandsAmerican adultsADAMTS4/5BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development
Shu B, Zhang M, Xie R, Wang M, Jin H, Hou W, Tang D, Harris SE, Mishina Y, O'Keefe RJ, Hilton MJ, Wang Y, Chen D. BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development. Journal Of Cell Science 2011, 124: 3428-3440. PMID: 21984813, PMCID: PMC3196857, DOI: 10.1242/jcs.083659.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone DevelopmentBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Cell DifferentiationCell Growth ProcessesCells, CulturedChondrocytesCore Binding Factor Alpha 1 SubunitCyclin-Dependent Kinase 4Gene Expression RegulationGrowth PlateMiceMice, KnockoutOsteochondrodysplasiasProtein Processing, Post-TranslationalSignal TransductionConceptsEndochondral bone developmentBMP4 geneCartilage developmentDeletion of Bmp2Post-transcriptional levelRunx2 protein levelsBone developmentChondrocyte proliferationChondrodysplasia phenotypeProteasomal degradationBMP2 geneGenetic controlKey regulatorConditional knockout miceMolecular mechanismsKnockout miceBMP2Chondrocyte differentiationGenesGrowth plate chondrocytesRunx2 expressionCartilage phenotypeSpecific functionsProfound defectsNovel insightsTGF‐β signaling plays an essential role in the growth and maintenance of intervertebral disc tissue
Jin H, Shen J, Wang B, Wang M, Shu B, Chen D. TGF‐β signaling plays an essential role in the growth and maintenance of intervertebral disc tissue. FEBS Letters 2011, 585: 1209-1215. PMID: 21420963, PMCID: PMC3090135, DOI: 10.1016/j.febslet.2011.03.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Density Conservation AgentsCells, CulturedChondrocytesCollagen Type IIFemaleGrowth PlateHistocytochemistryIntervertebral DiscMaleMatrix Metalloproteinase 13MiceMice, KnockoutMice, TransgenicProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaReverse Transcriptase Polymerase Chain ReactionSignal TransductionTamoxifenTime FactorsConceptsKnockout miceTgfbr2 conditional knockout miceMMP13 geneDisc tissueConditional knockout miceGrowth plate chondrocytesIntervertebral disc tissueAnnulus fibrosus cellsTGFBR2 geneTransgenic miceGrowth plate cartilagePostnatal stagesMiceNormal growth plate cartilagePlate cartilageDisc phenotypesDisc cellsNull backgroundPresent studyCartilage growthTissueCartilageCritical roleCellsEmbryonic stages
2010
Smad3 Prevents β-Catenin Degradation and Facilitates β-Catenin Nuclear Translocation in Chondrocytes*
Zhang M, Wang M, Tan X, Li TF, Zhang YE, Chen D. Smad3 Prevents β-Catenin Degradation and Facilitates β-Catenin Nuclear Translocation in Chondrocytes*. Journal Of Biological Chemistry 2010, 285: 8703-8710. PMID: 20097766, PMCID: PMC2838293, DOI: 10.1074/jbc.m109.093526.Peer-Reviewed Original ResearchConceptsBeta-catenin protein stabilityBeta-catenin nuclear translocationNuclear translocationDownstream target genesBeta-catenin proteinN-terminal regionDetailed molecular mechanismsΒ-catenin degradationTGF-beta/Smad3Β-catenin nuclear translocationProtein complexesProtein stabilityTarget genesRegulatory mechanismsSmad3 interactionMolecular mechanismsChondrocyte developmentDependent degradationNovel mechanismDependent mannerWntSmad3Growth factorTranslocationPathway