Roles of SATB2 in Osteogenic Differentiation and Bone Regeneration

Abstract

Expressed in branchial arches and osteoblast-lineage cells, special AT-rich sequence-binding protein (SATB2) is responsible for preventing craniofacial abnormalities and defects in osteoblast function. In this study, we transduced SATB2 into murine adult stem cells, and found that SATB2 significantly increased expression levels of bone matrix proteins, osteogenic transcription factors, and a potent angiogenic factor, vascular endothelial growth factor. Using an osterix (Osx) promoter-luciferase construct and calvarial cells isolated from runt-related transcription factor 2 (Runx2)-deficient mice, we found that SATB2 upregulates Osx expression independent of Runx2, but synergistically enhances the regulatory effect of Runx2 on Osx promoter. We then transplanted SATB2-overexpressing adult stem cells genetically double-labeled with bone sialoprotein (BSP) promoter-driven luciferase and β-actin promoter-driven enhanced green fluorescent protein into mandibular bone defects. We identified increased luciferase-positive cells in SATB2-overexpressing groups, indicating more transplanted cells undergoing osteogenic differentiation. New bone formation was consequently accelerated in SATB2 groups. In conclusion, SATB2 acts as a potent transcription factor to enhance osteoblastogenesis and promote bone regeneration. The application of SATB2 in bone tissue engineering gives rise to a higher bone forming capacity as a result of multiple-level amplification of regulatory activity.

Analysis of Differentiation Potentials and Gene Expression Profiles of Mesenchymal Stem Cells Derived from Periodontal Ligament and Wharton’s Jelly of the Umbilical Cord

“…SATB1 , SATB2 and TNFRSF11B , which are linked to ossification, were also up-regulated in PDLSCs. The SATB gene encodes a DNA-binding protein that spe-cifically binds nuclear matrix attachment regions, playing a critical role in bone generation and osteoblast differentiation ( table 2 ) [Savarese et al, 2009;Hassan et al, 2010;Zhang et al, 2011]. TNFRSF11B encodes the osteoblastsecreted decoy receptor protein and is a key negative regulator of osteoclastogenesis ( table 2 ) [Vidal et al, 2011].…”

MicroRNAs and post-transcriptional regulation of skeletal development

“…Coupling these osteoblast-specific transcription factors, Satb2 increases the transcription of Bglap by binding to its promoter (Dobreva et al 2006) and can also increase the expression of Ibsp by direct attachment to an osteoblast-specific promoter element (Dobreva et al 2006). In addition, although Dobreva et al did not find changes in Osx expression, others have reported that Satb2 acts in cooperation with Runx2 to upregulate Osx expression (Zhang et al 2011b). The miR-23a-27a-24-2 cluster inhibits osteogenesis in vitro by downregulating the expression of Satb2 through the direct binding of the three miRNAs to its 3 0 -UTR.…”

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

“…21 Overexpression of SATB2 promotes osteogenesis and improves bone mass in mice. 22 Genetically modified BMSCs are widely used in bone-tissue engineering. 23 We examined the cytotoxicity, apoptosis, and transfection efficiency of PEI 600 -β-CyD on primary rat MSCs and investigated the distribution of plasmids at 4 hours posttransfection by PEI 600 -β-CyD.…”