title: Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization.
abstract: Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application.
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.|KMEB, Department of Endocrinology, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
authors.forename: M
authors.identifier: 0000-0002-7096-998X
authors.initials: M
authors.lastname: Elsafadi
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Manikandan
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: R A
authors.initials: RA
authors.lastname: Dawud
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: N M
authors.initials: NM
authors.lastname: Alajez
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: R
authors.initials: R
authors.lastname: Hamam
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Alfayez
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.|KMEB, Department of Endocrinology, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.|KMEB, Department of Endocrinology, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.|Prince Naif Health Research Center, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Aldahmash
authors.affiliation: Stem Cells Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Mahmood
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D049109:Cell Proliferation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C051615:transgelin