Roles of SATB2 in Osteogenic Differentiation and Bone Regeneration

• Published in: Tissue engineering. Part A 2011-07, Vol.17 (13-14), p.1767-1776
• Main Authors: Zhang, Jin, Tu, Qisheng, Grosschedl, Rudolf, Kim, Min Seok, Griffin, Terrence, Drissi, Hicham, Yang, Pishan, Chen, Jake
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - metabolism; Animals; Bone diseases; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone Matrix - metabolism; Bone Regeneration - genetics; Cell Differentiation - genetics; Cell Line; Cells; Core Binding Factor Alpha 1 Subunit - metabolism; Dental Sac - cytology; DNA binding proteins; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Face; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; Luciferase; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - metabolism; Mice; Original; Original Articles; Osteogenesis - genetics; Physiological aspects; Proteins; Sp7 Transcription Factor; Stem cells; Stromal Cells - cytology; Stromal Cells - metabolism; Tissue engineering; Transcription Factors - genetics; Transcription Factors - metabolism; Up-Regulation - genetics
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2010.0503

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.