DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Kyu-Won | ko |
dc.contributor.author | Yook, Jin-Yong | ko |
dc.contributor.author | Son, Mi-Young | ko |
dc.contributor.author | Kim, Min-Jeong | ko |
dc.contributor.author | Koo, Deog-Bon | ko |
dc.contributor.author | Han, Yong Mahn | ko |
dc.contributor.author | Cho, Yee Sook | ko |
dc.date.accessioned | 2013-03-09T20:11:18Z | - |
dc.date.available | 2013-03-09T20:11:18Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2010-04 | - |
dc.identifier.citation | STEM CELLS AND DEVELOPMENT, v.19, no.4, pp.557 - 568 | - |
dc.identifier.issn | 1547-3287 | - |
dc.identifier.uri | http://hdl.handle.net/10203/97362 | - |
dc.description.abstract | Studies revealed that PI3K/AKT/mTOR signaling is important in the regulation of human embryonic stem cell (hESC) self-renewal and differentiation. However, its action on osteogenic differentiation of hESCs is poorly understood. We tested the effects of pharmacological PI3K/AKT/mTOR inhibitors on their potential to induce osteogenic differentiation of hESCs. Under feeder-free culture conditions, rapamycin (an mTOR inhibitor) potently inhibited the activities of mTOR and p70S6K in undifferentiated hESCs; however, LY294002 (a PI3K inhibitor) and an AKT inhibitor had no effects. Treatment with any of these inhibitors down-regulated the hESC markers Oct4 and Nanog, but only rapamycin induced the up-regulation of the early osteogenic markers BMP2 and Runx2. We also observed that hESCs differentiated when treated with FK506, a structural analog of rapamycin, but did not exhibit an osteogenic phenotype. Increases in Smad1/5/8 phosphorylation and Id1-4 mRNA expression indicated that rapamycin significantly stimulated BMP/Smad signaling. After inducing both hESCs and human embryoid bodies (hEBs) for 2-3 weeks with rapamycin, osteoblastic differentiation was further characterized by the expression of osteoblastic marker mRNAs and/or proteins (osterix, osteocalcin, osteoprotegerin, osteonectin, and bone sialoprotein), alkaline phosphatase activity, and alizarin red S staining for mineralized bone nodule formation. No significant differences in the osteogenic phenotypes of rapamycin-differentiated hESCs and hEBs were detected. Our results suggest that, among these 3 inhibitors, only rapamycin functions as a potent stimulator of osteoblastic differentiation of hESCs, and it does so by modulating rapamycin-sensitive mTOR and BMP/Smad signaling. | - |
dc.language | English | - |
dc.publisher | MARY ANN LIEBERT INC | - |
dc.subject | GROWTH-FACTOR-BETA | - |
dc.subject | IN-VITRO DIFFERENTIATION | - |
dc.subject | OSTEOGENIC DIFFERENTIATION | - |
dc.subject | ES CELLS | - |
dc.subject | ENHANCES OSTEOGENESIS | - |
dc.subject | 3-KINASE PATHWAY | - |
dc.subject | MOUSE | - |
dc.subject | LINEAGE | - |
dc.subject | PROLIFERATION | - |
dc.subject | PLURIPOTENCY | - |
dc.title | Rapamycin Promotes the Osteoblastic Differentiation of Human Embryonic Stem Cells by Blocking the mTOR Pathway and Stimulating the BMP/Smad Pathway | - |
dc.type | Article | - |
dc.identifier.wosid | 000276359200013 | - |
dc.identifier.scopusid | 2-s2.0-77950603770 | - |
dc.type.rims | ART | - |
dc.citation.volume | 19 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 557 | - |
dc.citation.endingpage | 568 | - |
dc.citation.publicationname | STEM CELLS AND DEVELOPMENT | - |
dc.contributor.localauthor | Han, Yong Mahn | - |
dc.contributor.nonIdAuthor | Lee, Kyu-Won | - |
dc.contributor.nonIdAuthor | Yook, Jin-Yong | - |
dc.contributor.nonIdAuthor | Son, Mi-Young | - |
dc.contributor.nonIdAuthor | Kim, Min-Jeong | - |
dc.contributor.nonIdAuthor | Koo, Deog-Bon | - |
dc.contributor.nonIdAuthor | Cho, Yee Sook | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | IN-VITRO DIFFERENTIATION | - |
dc.subject.keywordPlus | OSTEOGENIC DIFFERENTIATION | - |
dc.subject.keywordPlus | ES CELLS | - |
dc.subject.keywordPlus | ENHANCES OSTEOGENESIS | - |
dc.subject.keywordPlus | 3-KINASE PATHWAY | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordPlus | LINEAGE | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | PLURIPOTENCY | - |
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