Prolonged Application of High Fluid Shear to Chondrocytes Recapitulates Gene Expression Profiles Associated with Osteoarthritis 英文参考文献.docVIP

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Prolonged Application of High Fluid Shear to Chondrocytes Recapitulates Gene Expression Profiles Associated with Osteoarthritis 英文参考文献.doc

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Prolonged Application of High Fluid Shear to Chondrocytes Recapitulates Gene Expression Profiles Associated with Osteoarthritis 英文参考文献

ProlongedApplicationofHighFluidShearto ChondrocytesRecapitulatesGeneExpressionProfiles AssociatedwithOsteoarthritis FeiZhu1,PuWang1,NormanH.Lee2,MaryB.Goldring3,KonstantinosKonstantopoulos1,4* 1DepartmentofChemicalandBiomolecularEngineering,TheJohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica,2DepartmentofPharmacology and Physiology, The George Washington University Medical Center, Washington, D.C., United States of America, 3Hospital for Special Surgery, New York, New York, UnitedStatesofAmerica,4JohnsHopkinsPhysicalSciencesinOncologyCenterandInstituteforNanoBioTechnology,TheJohnsHopkinsUniversity,Baltimore,Maryland, UnitedStatesofAmerica Abstract Background:Excessivemechanicalloadingofarticularcartilageproducinghydrostaticstress,tensilestrainandfluidflow leadstoirreversiblecartilageerosionandosteoarthritic(OA)disease.Sinceapplicationofhighfluidsheartochondrocytes recapitulatessomeoftheearmarksofOA,weaimedtoscreenthegeneexpressionprofilesofshear-activatedchondrocytes andassesspotentialsimilaritieswithOAchondrocytes. Methodology/PrincipalFindings:UsingacDNAmicroarraytechnology,wescreenedthedifferentially-regulatedgenesin human T/C-28a2 chondrocytes subjected to high fluid shear (20dyn/cm2) for 48h and 72h relative to static controls. ConfirmationoftheexpressionpatternsofselectgeneswasobtainedbyqRT-PCR.Usingsignificanceanalysisofmicroarrays witha5%falsediscoveryrate,71and60non-redundanttranscriptswereidentifiedtobe$2-foldup-regulatedand#0.6- folddown-regulated,respectively,inshearedchondrocytes.Publisheddatasetsindicatethat42ofthesegenes,whichare related to extracellular matrix/degradation, cell proliferation/differentiation, inflammation and cell survival/death, are differentially-regulated in OA chondrocytes. In view of the pivotal role of cyclooxygenase-2 (COX-2) in the pathogenesis and/or progression of OA in vivo and regulation of shear-induced inflammation and apoptosis in vitro, we identified a collectionofgenesthatareeitherup-ordown-regulatedb