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 phenotypeMMP13 is a critical target gene during the progression of osteoarthritis
Wang M, Sampson ER, Jin H, Li J, Ke QH, Im HJ, Chen D. MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Research & Therapy 2013, 15: r5. PMID: 23298463, PMCID: PMC3672752, DOI: 10.1186/ar4133.Peer-Reviewed Original ResearchConceptsMeniscal-ligamentous injuryOA progressionControl miceMMP13 activityType II collagenTUNEL stainingCre-negative control miceChondrocyte apoptosisEffective disease-modifying treatmentTerminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainingTransferase dUTP nick end labeling stainingDUTP nick end labeling stainingRole of MMP13Nick end labeling stainingArticular cartilage lossCartilage gradingDisease-modifying treatmentsProgression of osteoarthritisWild-type miceDegenerative joint diseaseDevelopment of OAResults of immunohistochemistryEnd labeling stainingCre-negative miceArticular cartilage degeneration
2012
Lead 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 adultsADAMTS4/5