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dc.contributor.authorJia, Bingbingen_US
dc.contributor.authorMadsen, Liseen_US
dc.contributor.authorPetersen, Rasmus Koefoeden_US
dc.contributor.authorTecher, Nathalieen_US
dc.contributor.authorKopperud, Reidun Kristinen_US
dc.contributor.authorMa, Taoen_US
dc.contributor.authorDøskeland, Stein Oveen_US
dc.contributor.authorAilhaud, Gérarden_US
dc.contributor.authorWang, Jinfuen_US
dc.contributor.authorAmri, Ez-Zoubiren_US
dc.contributor.authorKristiansen, Karstenen_US
dc.PublishedPLoS ONE 7(3): e34114eng
dc.description.abstractHuman mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I2 (PGI2) may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX). Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK) was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells.en_US
dc.publisherPublic Library of Scienceeng
dc.rightsAttribution CC BYeng
dc.titleActivation of Protein Kinase A and Exchange Protein Directly Activated by cAMP Promotes Adipocyte Differentiation of Human Mesenchymal Stem Cellsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2012 Jia et al.

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