cAMPPKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKLOPG mRNA Expression in Mesenchymal Stem Cells by Suppressing Leptin 英文参考文献.docVIP

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cAMPPKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKLOPG mRNA Expression in Mesenchymal Stem Cells by Suppressing Leptin 英文参考文献.doc

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cAMPPKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKLOPG mRNA Expression in Mesenchymal Stem Cells by Suppressing Leptin 英文参考文献

cAMP/PKARegulatesOsteogenesis,Adipogenesisand RatioofRANKL/OPGmRNAExpressioninMesenchymal StemCellsbySuppressingLeptin Der-ChihYang1,4,Huey-JenTsay3,Shan-YangLin4,Shih-HwaChiou1,4,Mei-JaneLi4,Tai-JayChang4, Shih-ChiehHung1,2,4,5 * 1InstituteofClinicalMedicine,NationalYang-MingUniversity,Taipei,Taiwan,2InstituteofPharmacology,NationalYang-MingUniversity,Taipei,Taiwan,3Instituteof Neuroscience,NationalYang-MingUniversity,Taipei,Taiwan,4DepartmentofMedicalResearchandEducation,VeteransGeneralHospital-Taipei,NationalYang-Ming University,Taipei,Taiwan,5DepartmentofOrthopaedicsandTraumatology,VeteransGeneralHospital-Taipei,NationalYang-MingUniversity,Taipei,Taiwan Abstract Background:Mesenchymalstemcells(MSCs)areapluripotentcelltypethatcandifferentiateintoadipocytes,osteoblasts andothercells.Thereciprocalrelationshipbetweenadipogenesisandosteogenesiswaspreviouslydemonstrated;however, themechanismsremainlargelyunknown. MethodsandFindings:WereportthatactivationofPKAby3-isobutyl-1methylxanthine(IBMX)andforskolinenhances adipogenesis,thegeneexpressionofPPARc2andLPL,anddownregulatesthegeneexpressionofRunx2andosteopontin, markers of osteogenesis. PKA activation also decreases the ratio of Receptor Activator of the NF-kB Ligand to Osteoprotegerin(RANKL/OPG)geneexpression–thekeyfactorsofosteoclastogenesis.Alltheseeffectsaremediatedbythe cAMP/PKA/CREB pathway by suppressing leptin, and may contribute to PKA stimulators-induced in vivo bone loss in developingzebrafish. Conclusions:UsingMSCs,thecenterofanewlyproposedbonemetabolicunit,weidentifiedcAMP/PKAsignaling,oneof the many signaling pathways that regulate bone homeostasis via controlling cyto-differentiation of MSCs and altering RANKL/OPGgeneexpression. Citation:YangD-C,TsayH-J,LinS-Y,ChiouS-H,LiM-J,etal(2008)cAMP/PKARegulatesOsteogenesis,AdipogenesisandRatioofRANKL/OPGmRNAExpression inMesenchymalStemCellsbySuppressingLeptin.PLoSONE3(2):e1540.doi:10.1371/journal.pone.0001540 Editor:NeilHotchin,UniversityofBirmingham,UnitedKin