The transcription factor Sox2 is required for osteoblast self-renewal

Abstract

The development and maintenance of most tissues and organs requires the presence of multipotent and unipotent stem cells that have the ability of self-renewal as well as of generating committed, further differentiated cell types. The transcription factor Sox2 is essential for embryonic development and maintains pluripotency and self-renewal in embryonic stem cells. It is expressed in immature osteoblasts/osteoprogenitors in vitro and in vivo and is induced by FGF signaling, which stimulates osteoblast proliferation and inhibits differentiation. Sox2 overexpression can by itself inhibit osteoblast differentiation. To elucidate its role in the osteoblastic lineage, we generated mice with an osteoblast-specific, Cre-mediated knockout of Sox2. These mice are small and osteopenic, and mosaic for Sox2 inactivation. However, culturing calvarial osteoblasts from the mutant mice for 2-3 passages failed to yield any Sox2 null cells. Inactivation of the Sox2 gene by Cre-mediated excision in cultured osteoblasts showed that Sox2 null cells could not survive repeated passage in culture, could not form colonies, and arrested their growth with a senescent phenotype. Additionally, expression of Sox2 specific shRNAs in independent osteoblastic cell lines suppressed their proliferative ability. Osteoblasts capable of forming “osteospheres” are greatly enriched in Sox2 expression. These data identify a novel role for Sox2 in the maintenance of self-renewal in the osteoblastic lineage.

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

“…Recently, a novel function for Sox2 was identified in a mouse osteoblastic lineage: the maintenance of the self-renewal of cells. In addition, Sox2-knockout cells could not form colonies, and their population growth was arrested with a senescent phenotype (Basu-Roy et al, 2010). In another study, most Sox2-overexpressed BMSCs were small and showed high proliferative and osteogenic capabilities from human BMSCs (Go et al, 2008).…”

Sox2 is required for embryonic development of the ventral telencephalon through the activation of the ventral determinants Nkx2.1 and Shh

“…The Sox2 transcription factor is crucial for the maintenance of several types of stem cells, including pluripotent, neural and osteogenic stem cells (Masui et al, 2007;Favaro et al, 2009;Basu Roy et al, 2010). Despite the importance of Sox2 in NSCs in vitro, major abnormalities in brain development were not detected by conditional ablation of Sox2 at midgestation (E12.5) in mouse, with the exception of defects in postnatal development of the hippocampus dentate gyrus and of the retina (Taranova et al, 2006;Miyagi et al, 2008;Favaro et al, 2009).…”

“…Later in development, Sox2 is required in various tissue stem cells and early progenitors, in particular in the nervous system (Que et al, 2009;Basu-Roy et al, 2010;Pevny and Nicolis, 2010). Throughout vertebrate evolution, Sox2 is expressed in the developing neuroectoderm from its earliest stages (Wegner and Stolt, 2005).…”

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

“…The transcription factor Sox2, a member of the SY-related, HMG box family, plays a critical role in embryonic development and maintenance of pluripotency and self-renewal of embryonic stem cells [29,30]. Furthermore, Sox2 is also involved in the maintenance of self-renewal of the osteoblastic lineage [31]. Recently, it was shown that mesenchymal stem cells derived from human umbilical cord constitutively express SOX2 and are capable of differentiating into osteoblast as well as adipocytes, indicating the involvement of SOX2 in osteoblast differentiation [32].…”