dc.contributor.author
Elsafadi, M.
dc.contributor.author
Manikandan, M.
dc.contributor.author
Dawud, R. A.
dc.contributor.author
Alajez, N. M.
dc.contributor.author
Hamam, R.
dc.contributor.author
Alfayez, M.
dc.contributor.author
Kassem, M.
dc.contributor.author
Aldahmash, A.
dc.contributor.author
Mahmood, A.
dc.date.accessioned
2018-06-08T03:37:47Z
dc.date.available
2016-09-20T08:44:01.104Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/15592
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19780
dc.description.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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic
differentiation of human skeletal stem cells through actin cytoskeleston
organization
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Cell Death and Disease. - 7 (2016), Artikel Nr. e2321
dcterms.bibliographicCitation.doi
10.1038/cddis.2016.196
dcterms.bibliographicCitation.url
http://www.nature.com/cddis/journal/v7/n8/full/cddis2016196a.html
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000025397
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006985
dcterms.accessRights.openaire
open access