Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells

Dalia Ayesh Hafez Ali, Sarah Abuelreich, Nora Alkeraishan, Najla Bin Shwish, Rimi Hamam, Moustapha Kassem, Musaad Alfayez, Abdullah Aldahmash, Nehad M Alajez

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

115 Downloads (Pure)

Resumé

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.

OriginalsprogEngelsk
ArtikelnummerBSR20171252
TidsskriftBioscience Reports
Vol/bind38
Udgave nummer1
Antal sider10
ISSN0144-8463
DOI
StatusUdgivet - 30. jan. 2018

Fingeraftryk

Stem cells
Mesenchymal Stromal Cells
Adipocytes
Bone
Metabolism
Genes
dimethylaniline monooxygenase (N-oxide forming)
Cells
Ketone Bodies
Adipogenesis
Focal Adhesions
Benzo(a)pyrene
Insulin Receptor
Gene Expression Profiling
Selenium
Metabolic Networks and Pathways
Gene expression
Tryptophan
Energy Metabolism
Cell Survival

Citer dette

Ayesh Hafez 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. I: Bioscience Reports. 2018 ; Bind 38, Nr. 1.
@article{401ebac6cae34e61bde3ab8df50b25f2,
title = "Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells",
abstract = "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.",
keywords = "Journal Article",
author = "{Ayesh Hafez Ali}, Dalia and Sarah Abuelreich and Nora Alkeraishan and Shwish, {Najla Bin} and Rimi Hamam and Moustapha Kassem and Musaad Alfayez and Abdullah Aldahmash and Alajez, {Nehad M}",
note = "{\circledC} 2018 The Author(s).",
year = "2018",
month = "1",
day = "30",
doi = "10.1042/BSR20171252",
language = "English",
volume = "38",
journal = "Bioscience Reports",
issn = "0144-8463",
publisher = "Portland Press Ltd.",
number = "1",

}

Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells. / Ayesh Hafez Ali, Dalia; Abuelreich, Sarah; Alkeraishan, Nora; Shwish, Najla Bin; Hamam, Rimi; Kassem, Moustapha; Alfayez, Musaad; Aldahmash, Abdullah; Alajez, Nehad M.

I: Bioscience Reports, Bind 38, Nr. 1, BSR20171252, 30.01.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells

AU - Ayesh Hafez Ali, Dalia

AU - Abuelreich, Sarah

AU - Alkeraishan, Nora

AU - Shwish, Najla Bin

AU - Hamam, Rimi

AU - Kassem, Moustapha

AU - Alfayez, Musaad

AU - Aldahmash, Abdullah

AU - Alajez, Nehad M

N1 - © 2018 The Author(s).

PY - 2018/1/30

Y1 - 2018/1/30

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1042/BSR20171252

DO - 10.1042/BSR20171252

M3 - Journal article

C2 - 29298881

VL - 38

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 1

M1 - BSR20171252

ER -