title: Role of Slug transcription factor in human mesenchymal stem cells.
abstract: The pathways that control mesenchymal stem cells (MSCs) differentiation are not well understood, and although some of the involved transcription factors (TFs) have been characterized, the role of others remains unclear. We used human MSCs from tibial plateau (TP) trabecular bone, iliac crest (IC) bone marrow and Wharton's jelly (WJ) umbilical cord demonstrating a variability in their mineral matrix deposition, and in the expression levels of TFs including Runx2, Sox9, Sox5, Sox6, STAT1 and Slug, all involved in the control of osteochondroprogenitors differentiation program. Because we reasoned that the basal expression level of some TFs with crucial role in the control of MSC fate may be correlated with osteogenic potential, we considered the possibility to affect the hMSCs behaviour by using gene silencing approach without exposing cells to induction media. In this study we found that Slug-silenced cells changed in morphology, decreased in their migration ability, increased Sox9 and Sox5 and decreased Sox6 and STAT1 expression. On the contrary, the effect of Slug depletion on Runx2 was influenced by cell type. Interestingly, we demonstrated a direct in vivo regulatory action of Slug by chromatin immunoprecipitation, showing a specific recruitment of this TF in the promoter of Runx2 and Sox9 genes. As a whole, our findings have important potential implication on bone tissue engineering applications, reinforcing the concept that manipulation of specific TF expression levels may elucidate MSC biology and the molecular mechanisms, which promote osteogenic differentiation.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Torreggiani
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
authors.forename: Cristina
authors.initials: C
authors.lastname: Manferdini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lambertini
authors.forename: Letizia
authors.initials: L
authors.lastname: Penolazzi
authors.forename: Renata
authors.initials: R
authors.lastname: Vecchiatini
authors.forename: Elena
authors.initials: E
authors.lastname: Gabusi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Chieco
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Roberta
authors.initials: R
authors.lastname: Piva
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D017931:DNA Primers; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; C000604407:SNAI1 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors