Roles of SATB2 in Osteogenic Differentiation and Bone Regeneration
Roles of SATB2 in Osteogenic Differentiation and Bone Regeneration
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DOI：
10.1089/ten.tea.2010.0503
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发表时间：
2011-07-01
影响因子：
4.1
通讯作者：
Chen, Jake
中科院分区：
文献类型：
--
作者：
Zhang, Jin;Tu, Qisheng;Chen, Jake
在鳃弓和成骨细胞系细胞中表达的特殊的富含AT的序列结合蛋白（SATB 2）负责预防颅面畸形和成骨细胞功能缺陷。在这项研究中，我们将SATB 2转导到小鼠成体干细胞中，发现SATB 2显著增加了骨基质蛋白、成骨转录因子和有效的血管生成因子血管内皮生长因子的表达水平。使用osterix（Osx）启动子-荧光素酶构建体和从runt相关转录因子2（Runx 2）缺陷小鼠分离的颅骨细胞，我们发现SATB 2上调Osx表达独立于Runx 2，但协同增强Runx 2对Osx启动子的调节作用。然后，我们将SATB 2过表达的成体干细胞移植到下颌骨缺损中，所述成体干细胞用骨唾液蛋白（BSP）启动子驱动的荧光素酶和β-肌动蛋白启动子驱动的增强型绿色荧光蛋白进行遗传双标记。我们发现在SATB 2过表达组中，磷酸化酶阳性细胞增加，表明更多的移植细胞进行成骨分化。因此，在SATB 2组中，新骨形成加速。总之，SATB 2作为一个有效的转录因子，以增强成骨细胞和促进骨再生。SATB 2在骨组织工程中的应用，由于调节活性的多水平放大，导致更高的成骨能力。
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 beta-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.