Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors 英文参考文献.docVIP

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Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors 英文参考文献.doc

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Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors 英文参考文献

CellAdhesionSignalingRegulatesRANKExpressionin OsteoclastPrecursors AyakoMochizuki1,2,MasamichiTakami1*,YoichiMiyamoto1,TsuyoshiNakamaki3,ShigeruTomoyasu3, YuhoKadono4,SakaeTanaka4,TomioInoue2,RyutaroKamijo1 1DepartmentofBiochemistry,SchoolofDentistry,ShowaUniversity,Shinagawa,Tokyo,Japan,2DepartmentofOralPhysiology,SchoolofDentistry,ShowaUniversity, Shinagawa, Tokyo, Japan, 3Division of Hematology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan, 4Department of OrthopaedicSurgery,FacultyofMedicine,TheUniversityofTokyo,Bunkyo,Tokyo,Japan Abstract Cells with monocyte/macrophage lineage expressing receptor activator of NF-kB (RANK) differentiate into osteoclasts followingstimulationwiththeRANKligand(RANKL).Celladhesionsignalingisalsorequiredforosteoclastdifferentiation fromprecursors.However,detailsofthemechanismbywhichcelladhesionsignalsinduceosteoclastdifferentiationhave not been fully elucidated. To investigate the participation of cell adhesion signaling in osteoclast differentiation, mouse bonemarrow-derivedmacrophages(BMMs)wereusedasosteoclastprecursors,andculturedoneitherplasticcellculture dishes (adherent condition) or the top surface of semisolid methylcellulose gel loaded in culture tubes (non-adherent condition).BMMsculturedundertheadherentconditiondifferentiatedintoosteoclastsinresponsetoRANKLstimulation. However,underthenon-adherentcondition,theefficiencyofosteoclastdifferentiationwasmarkedlyreducedeveninthe presenceofRANKL.TheseBMMsretainedmacrophagecharacteristicsincludingphagocyticfunctionandgeneexpression profile. Lipopolysaccharide (LPS) and tumor necrosis factor –aTNF-a activated the NF-kB-mediated signaling pathways under both the adherent and non-adherent conditions, while RANKL activated the pathways only under the adherent condition.BMMshighlyexpressedRANKmRNAandproteinundertheadherentconditionascomparedtothenon-adherent condition.Also,BMMstransferredfromtheadherenttonon-adherentconditionshoweddownregulated