2015
Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing
Wang M, Nasiri AR, Broadus AE, Tommasini SM. Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing. Bone 2015, 81: 104-111. PMID: 26164475, PMCID: PMC4641003, DOI: 10.1016/j.bone.2015.07.008.Peer-Reviewed Original ResearchConceptsFracture healingPTHrP expressionCKO miceCortical bone surfaceFracture repairTibial fracture surgeryRole of PTHrPHormone-related proteinTibial fracture modelCartilaginous callus formationConditional knockout miceBone surfaceCortical bone remodelingType I receptorCD1 controlsFracture surgeryCD1 miceKnockout miceInitial genetic evidencePTHrPOsteoblastic activityBone remodelingMiceBone mineralizationI receptor
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 geneTMJADAMTS5MMP13Periosteal PTHrP regulates cortical bone modeling during linear growth in mice
Wang M, VanHouten JN, Nasiri AR, Tommasini SM, Broadus AE. Periosteal PTHrP regulates cortical bone modeling during linear growth in mice. Journal Of Anatomy 2014, 225: 71-82. PMID: 24762197, PMCID: PMC4073294, DOI: 10.1111/joa.12184.Peer-Reviewed Original ResearchConceptsMetaphyseal-diaphyseal junctionParathyroid hormone-related peptideEndocortical bone formationCD-1 miceNF-kB ligandHormone-related peptideMineral apposition rateCortical bone modelingEntire boneLinear growthAnteromedial cortexCKO miceProximal tibiaLateral tibiaReceptor activatorOC numberApposition rateOsteoclastic resorptionPTHrPBone modelingBone formationFibulaLong bonesMicePeriosteum
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 phenotypeThe remarkable migration of the medial collateral ligament
Wang M, Nasiri A, VanHouten JN, Tommasini SM, Broadus AE. The remarkable migration of the medial collateral ligament. Journal Of Anatomy 2013, 224: 490-498. PMID: 24266550, PMCID: PMC3954274, DOI: 10.1111/joa.12145.Peer-Reviewed Original ResearchConceptsMedial collateral ligamentMigratory tractsCollateral ligamentParathyroid hormone-related proteinOsteoclastic bone resorptionHormone-related proteinCortical surfaceInsertions of tendonsInsertion siteBone resorptionLong bone growthPTHrP functionsOsteoclastic activityPeriosteal osteoclastsRegulatory moleculesOsteoblast activityGrowth spurtLong bonesOsteoclastsCortical boneLigamentRecent evidenceHistological techniquesBone surfaceTractMMP13 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
PTHrP regulates the modeling of cortical bone surfaces at fibrous insertion sites during growth
Wang M, VanHouten JN, Nasiri AR, Johnson RL, Broadus AE. PTHrP regulates the modeling of cortical bone surfaces at fibrous insertion sites during growth. Journal Of Bone And Mineral Research 2012, 28: 598-607. PMID: 23109045, PMCID: PMC3574208, DOI: 10.1002/jbmr.1801.Peer-Reviewed Original ResearchConceptsCortical bone surfaceCortical surfaceParathyroid hormone-related proteinLong bonesHormone-related proteinMedial collateral ligamentBone cell activityBone surfaceLong bone growthTendon insertionForme frusteCollateral ligamentFibrous enthesesInitial genetic evidenceCell activityInsertion sitePTHrPConditional deletionLinear growthEnthesesLigamentPeriosteal componentBiomechanical controlBoneFrusteConditional 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 ablation
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 insightsSmad1 plays an essential role in bone development and postnatal bone formation
Wang M, Jin H, Tang D, Huang S, Zuscik MJ, Chen D. Smad1 plays an essential role in bone development and postnatal bone formation. Osteoarthritis And Cartilage 2011, 19: 751-762. PMID: 21420501, PMCID: PMC3113680, DOI: 10.1016/j.joca.2011.03.004.Peer-Reviewed Original ResearchConceptsPostnatal bone formationBone developmentCKO miceAlkaline phosphatase activityCalvarial bone developmentRole of Smad1Essential roleGene expression analysisBone formationOsteoblast-specific deletionCol2a1-Cre transgenic miceTransgenic miceBMP signalingSmad1 geneRelative gene expressionExpression analysisGene expressionConditional knockout miceOsteopenic phenotypeSmad1Formation assaysPhosphatase activityPrimary cellsOsteoblast proliferationKnockout miceTGF‐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