TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton

Mona Elsafadi, Muthurangan Manikandan, Sami Almalki, Mohammad Mobarak, Muhammad Atteya, Zafar Iqbal, Jamil Amjad Hashmi, Sameerah Shaheen, Nehad Alajez, Musaad Alfayez, Moustapha Kassem, Raed Abu Dawud, Amer Mahmood

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Resumé

TGFβis a potent regulator of several biological functions in many cell types, but its role in the differentiation of human bone marrow-derived skeletal stem cells (hMSCs) is currently poorly understood. In the present study, we demonstrate that a single dose of TGFβ1 prior to induction of osteogenic or adipogenic differentiation results in increased mineralized matrix or increased numbers of lipid-filled mature adipocytes, respectively. To identify the mechanisms underlying this TGFβ-mediated enhancement of lineage commitment, we compared the gene expression profiles of TGFβ1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGFβl treatment was associated with an enrichment of genes in the skeletal and extracellular matrix categories and the regulation of the actin cytoskeleton. To investigate further, we examined the actin cytoskeleton following treatment with TGFβ1 and/or cytochalasin D. Interestingly, cytochalasin D treatment of hMSCs enhanced adipogenic differentiation but inhibited osteogenic differentiation. Global gene expression profiling revealed a significant enrichment of pathways related to osteogenesis and adipogenesis and of genes regulated by both TGFβ1 and cytochalasin D. Our study demonstrates that TGFβ1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.

OriginalsprogEngelsk
Artikelnummer6913594
TidsskriftStem Cells International
Vol/bind2018
Antal sider14
ISSN1687-966X
DOI
StatusUdgivet - 2018

Fingeraftryk

Cytochalasin D
Adipogenesis
Gene Expression Profiling
Computational Biology
Transcriptome
Adipocytes
Osteogenesis
Down-Regulation
Lipids

Citer dette

Elsafadi, Mona ; Manikandan, Muthurangan ; Almalki, Sami ; Mobarak, Mohammad ; Atteya, Muhammad ; Iqbal, Zafar ; Hashmi, Jamil Amjad ; Shaheen, Sameerah ; Alajez, Nehad ; Alfayez, Musaad ; Kassem, Moustapha ; Dawud, Raed Abu ; Mahmood, Amer. / TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton. I: Stem Cells International. 2018 ; Bind 2018.
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title = "TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton",
abstract = "TGFβis a potent regulator of several biological functions in many cell types, but its role in the differentiation of human bone marrow-derived skeletal stem cells (hMSCs) is currently poorly understood. In the present study, we demonstrate that a single dose of TGFβ1 prior to induction of osteogenic or adipogenic differentiation results in increased mineralized matrix or increased numbers of lipid-filled mature adipocytes, respectively. To identify the mechanisms underlying this TGFβ-mediated enhancement of lineage commitment, we compared the gene expression profiles of TGFβ1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGFβl treatment was associated with an enrichment of genes in the skeletal and extracellular matrix categories and the regulation of the actin cytoskeleton. To investigate further, we examined the actin cytoskeleton following treatment with TGFβ1 and/or cytochalasin D. Interestingly, cytochalasin D treatment of hMSCs enhanced adipogenic differentiation but inhibited osteogenic differentiation. Global gene expression profiling revealed a significant enrichment of pathways related to osteogenesis and adipogenesis and of genes regulated by both TGFβ1 and cytochalasin D. Our study demonstrates that TGFβ1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.",
author = "Mona Elsafadi and Muthurangan Manikandan and Sami Almalki and Mohammad Mobarak and Muhammad Atteya and Zafar Iqbal and Hashmi, {Jamil Amjad} and Sameerah Shaheen and Nehad Alajez and Musaad Alfayez and Moustapha Kassem and Dawud, {Raed Abu} and Amer Mahmood",
year = "2018",
doi = "10.1155/2018/6913594",
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volume = "2018",
journal = "Stem Cells International",
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Elsafadi, M, Manikandan, M, Almalki, S, Mobarak, M, Atteya, M, Iqbal, Z, Hashmi, JA, Shaheen, S, Alajez, N, Alfayez, M, Kassem, M, Dawud, RA & Mahmood, A 2018, 'TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton', Stem Cells International, bind 2018, 6913594. https://doi.org/10.1155/2018/6913594

TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton. / Elsafadi, Mona; Manikandan, Muthurangan; Almalki, Sami; Mobarak, Mohammad; Atteya, Muhammad; Iqbal, Zafar; Hashmi, Jamil Amjad; Shaheen, Sameerah; Alajez, Nehad; Alfayez, Musaad; Kassem, Moustapha; Dawud, Raed Abu; Mahmood, Amer.

I: Stem Cells International, Bind 2018, 6913594, 2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton

AU - Elsafadi, Mona

AU - Manikandan, Muthurangan

AU - Almalki, Sami

AU - Mobarak, Mohammad

AU - Atteya, Muhammad

AU - Iqbal, Zafar

AU - Hashmi, Jamil Amjad

AU - Shaheen, Sameerah

AU - Alajez, Nehad

AU - Alfayez, Musaad

AU - Kassem, Moustapha

AU - Dawud, Raed Abu

AU - Mahmood, Amer

PY - 2018

Y1 - 2018

N2 - TGFβis a potent regulator of several biological functions in many cell types, but its role in the differentiation of human bone marrow-derived skeletal stem cells (hMSCs) is currently poorly understood. In the present study, we demonstrate that a single dose of TGFβ1 prior to induction of osteogenic or adipogenic differentiation results in increased mineralized matrix or increased numbers of lipid-filled mature adipocytes, respectively. To identify the mechanisms underlying this TGFβ-mediated enhancement of lineage commitment, we compared the gene expression profiles of TGFβ1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGFβl treatment was associated with an enrichment of genes in the skeletal and extracellular matrix categories and the regulation of the actin cytoskeleton. To investigate further, we examined the actin cytoskeleton following treatment with TGFβ1 and/or cytochalasin D. Interestingly, cytochalasin D treatment of hMSCs enhanced adipogenic differentiation but inhibited osteogenic differentiation. Global gene expression profiling revealed a significant enrichment of pathways related to osteogenesis and adipogenesis and of genes regulated by both TGFβ1 and cytochalasin D. Our study demonstrates that TGFβ1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.

AB - TGFβis a potent regulator of several biological functions in many cell types, but its role in the differentiation of human bone marrow-derived skeletal stem cells (hMSCs) is currently poorly understood. In the present study, we demonstrate that a single dose of TGFβ1 prior to induction of osteogenic or adipogenic differentiation results in increased mineralized matrix or increased numbers of lipid-filled mature adipocytes, respectively. To identify the mechanisms underlying this TGFβ-mediated enhancement of lineage commitment, we compared the gene expression profiles of TGFβ1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGFβl treatment was associated with an enrichment of genes in the skeletal and extracellular matrix categories and the regulation of the actin cytoskeleton. To investigate further, we examined the actin cytoskeleton following treatment with TGFβ1 and/or cytochalasin D. Interestingly, cytochalasin D treatment of hMSCs enhanced adipogenic differentiation but inhibited osteogenic differentiation. Global gene expression profiling revealed a significant enrichment of pathways related to osteogenesis and adipogenesis and of genes regulated by both TGFβ1 and cytochalasin D. Our study demonstrates that TGFβ1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.

U2 - 10.1155/2018/6913594

DO - 10.1155/2018/6913594

M3 - Journal article

C2 - 29535777

VL - 2018

JO - Stem Cells International

JF - Stem Cells International

SN - 1687-966X

M1 - 6913594

ER -