title: Sox2 is a potent inhibitor of osteogenic and adipogenic differentiation in human mesenchymal stem cells.
abstract: Human mesenchymal stem cells (hMSCs) are a promising target for cell-based bone regeneration. However, their application for clinical use is limited because hMSCs lose their ability for cell division and differentiation during longer in vitro cultivation. The osteogenic differentiation is regulated through a complex network of molecular signal transduction pathways where the canonical Wnt pathway plays an important role. Sox2, a known key factor for maintenance of cellular pluripotency in stem cells, is supposed to influence the Wnt pathway in osteoblasts. In this study, we overexpressed Sox2 in immortalized hMSCs by lentiviral gene transfer. Sox2 overexpression significantly reduced the osteogenic and adipogenic differentiation potentials. This effect was abolished by knockdown of Sox2 overexpression. In addition, Oct4 and Nanog, other key transcription factors for pluripotency, are strongly upregulated when Sox2 is overexpressed. Furthermore, Dkk1, a target gene of the Sox2-Oct4 heterodimer and a Wnt antagonist, is downregulated. Sox2 overexpression causes higher expression levels of β-catenin, the central transcription factor of the canonical Wnt pathway. These results suggest that Sox2 keeps hMSCs in an undifferentiated state by influencing the canonical Wnt pathway. Regulated expression of Sox2 may be a promising tool to cultivate hMSCs in sufficient quantities for cell and gene therapy applications.
authors.affiliation: 1 Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University , 80336, Munich, Germany .
authors.forename: Veronika
authors.initials: V
authors.lastname: Schönitzer
authors.forename: Roman
authors.initials: R
authors.lastname: Wirtz
authors.forename: Veronika
authors.initials: V
authors.lastname: Ulrich
authors.forename: Tamara
authors.initials: T
authors.lastname: Berger
authors.forename: Angelika
authors.initials: A
authors.lastname: Karl
authors.forename: Wolf
authors.initials: W
authors.lastname: Mutschler
authors.forename: Matthias
authors.initials: M
authors.lastname: Schieker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Böcker
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors