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Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells
Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling d...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789155/ https://www.ncbi.nlm.nih.gov/pubmed/29298881 http://dx.doi.org/10.1042/BSR20171252 |
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author | Ali, Dalia Abuelreich, Sarah Alkeraishan, Nora Shwish, Najla Bin Hamam, Rimi Kassem, Moustapha Alfayez, Musaad Aldahmash, Abdullah Alajez, Nehad M. |
author_facet | Ali, Dalia Abuelreich, Sarah Alkeraishan, Nora Shwish, Najla Bin Hamam, Rimi Kassem, Moustapha Alfayez, Musaad Aldahmash, Abdullah Alajez, Nehad M. |
author_sort | Ali, Dalia |
collection | PubMed |
description | Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27–58% inhibition, P<0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis. |
format | Online Article Text |
id | pubmed-5789155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57891552018-02-09 Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells Ali, Dalia Abuelreich, Sarah Alkeraishan, Nora Shwish, Najla Bin Hamam, Rimi Kassem, Moustapha Alfayez, Musaad Aldahmash, Abdullah Alajez, Nehad M. Biosci Rep Research Articles Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27–58% inhibition, P<0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis. Portland Press Ltd. 2018-01-30 /pmc/articles/PMC5789155/ /pubmed/29298881 http://dx.doi.org/10.1042/BSR20171252 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Ali, Dalia Abuelreich, Sarah Alkeraishan, Nora Shwish, Najla Bin Hamam, Rimi Kassem, Moustapha Alfayez, Musaad Aldahmash, Abdullah Alajez, Nehad M. Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title | Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title_full | Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title_fullStr | Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title_full_unstemmed | Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title_short | Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
title_sort | multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789155/ https://www.ncbi.nlm.nih.gov/pubmed/29298881 http://dx.doi.org/10.1042/BSR20171252 |
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