TGF β 1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton.

Autor: Elsafadi M; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; KMEB, Department of Endocrinology, University Hospital of Odense, Odense, Denmark.; KMEB, Department of Endocrinology, University of Southern Denmark, Odense, Denmark., Manikandan M; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Almalki S; College of Agriculture, King Saud University, Riyadh, Saudi Arabia., Mobarak M; Department of Histopathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Atteya M; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt., Iqbal Z; Department of Basic Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), National Guard Health Affairs, Al Ahsa, Saudi Arabia., Hashmi JA; Center for Genetics and Inherited Diseases, Taibah University, Medina, Al Madinah, Saudi Arabia., Shaheen S; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Alajez N; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Alfayez M; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Kassem M; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; KMEB, Department of Endocrinology, University Hospital of Odense, Odense, Denmark.; KMEB, Department of Endocrinology, University of Southern Denmark, Odense, Denmark., Dawud RA; Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Mahmood A; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: Stem cells international [Stem Cells Int] 2018 Feb 15; Vol. 2018, pp. 6913594. Date of Electronic Publication: 2018 Feb 15 (Print Publication: 2018).
DOI: 10.1155/2018/6913594
Abstrakt: TGF β is 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 TGF β 1 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 TGF β -mediated enhancement of lineage commitment, we compared the gene expression profiles of TGF β 1-treated hMSC cultures using DNA microarrays. In total, 1932 genes were upregulated, and 1298 genes were downregulated. Bioinformatics analysis revealed that TGF β l 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 TGF β 1 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 TGF β 1 and cytochalasin D. Our study demonstrates that TGF β 1 enhances hMSC commitment to either the osteogenic or adipogenic lineages by reorganizing the actin cytoskeleton.
Databáze: MEDLINE
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