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特殊富含 AT 序列结合蛋白 2 在人牙髓间充质干细胞成骨中的作用。

Role of Special AT-Rich Sequence-Binding Protein 2 in the Osteogenesis of Human Dental Mesenchymal Stem Cells.

机构信息

Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.

Department of Pediatric Dentistry, The Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing, China.

出版信息

Stem Cells Dev. 2020 Aug;29(16):1059-1072. doi: 10.1089/scd.2020.0013. Epub 2020 Jun 25.

DOI:10.1089/scd.2020.0013
PMID:32484035
Abstract

Dental mesenchymal stem cells (MSCs) are recognized as a critical factor in repair of defective craniofacial bone owing to the multiple differentiation potential, the ability to regenerate distinct tissues, and the advantage that they can be easily obtained by relatively noninvasive procedures. Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix protein, involved in chromatin remodeling and transcriptional regulation, and has been reported to be as a positive regulator of osteoblast differentiation, bone formation, and bone regeneration in MSCs. In this study, we systematically investigated the capability of SATB2 to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and stem cells from human exfoliated deciduous teeth (SHED). RNA-seq analysis and quantitative real-time PCR (RT-PCR) revealed that genes regulating osteogenic differentiation were differentially expressed among three cell types and SATB2 was found to be expressed at a relatively high level. When the three cell types overexpressed SATB2 with AdSATB2 infection, alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red S staining, and quantification tended to increase with an increasing infection rate. It showed opposite results after infection with AdsiSATB2. RNA-seq analysis indicated that the expression of downstream osteogenic genes was affected by AdSATB2 infection and quantitative RT-PCR confirmed that nine osteogenic genes (, , , , , , , , and ) were upregulated, to various extents, following SATB2 overexpression. In addition, quantitative PCR results indicated that SATB2 affected the expression of MSC markers. These results suggested an important role of SATB2 in the osteogenesis of PDLSCs, DPSCs, and SHED. Further research is warranted to investigate SATB2-mediated regulation of osteogenic differentiation and to evaluate the therapeutic use of SATB2 for the regeneration of defective craniofacial bone tissue.

摘要

牙髓干细胞(DPSCs)和成牙本质细胞间充质干细胞(DPSC)是一种间充质干细胞,具有多向分化潜能、再生不同组织的能力,并且可以通过相对无创的程序容易地获得,被认为是修复缺损颅面骨的关键因素。特殊富含 AT 的序列结合蛋白 2(SATB2)是一种核基质蛋白,参与染色质重塑和转录调控,并已被报道为成骨细胞分化、骨形成和骨再生的正调节剂。在这项研究中,我们系统地研究了 SATB2 促进牙周膜干细胞(PDLSCs)、牙髓干细胞(DPSCs)和成牙本质细胞间充质干细胞(SHED)成骨分化的能力。RNA-seq 分析和实时定量 PCR(RT-PCR)显示,三种细胞类型中调节成骨分化的基因表达水平不同,并且 SATB2 的表达水平相对较高。当三种细胞类型通过 AdSATB2 感染过表达 SATB2 时,碱性磷酸酶(ALP)染色、ALP 活性、茜素红 S 染色和定量分析均呈现随感染率增加而增加的趋势。而感染 AdsiSATB2 时则出现相反的结果。RNA-seq 分析表明,AdSATB2 感染影响下游成骨基因的表达,实时定量 RT-PCR 证实,SATB2 过表达后,九个成骨基因(、、、、、、、和)的表达均不同程度地上调。此外,定量 PCR 结果表明 SATB2 影响 MSC 标志物的表达。这些结果表明 SATB2 在 PDLSCs、DPSCs 和 SHED 的成骨作用中起重要作用。需要进一步研究 SATB2 对成骨分化的调节作用,并评估 SATB2 用于再生缺损颅面骨组织的治疗用途。

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引用本文的文献

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Int J Oral Sci. 2025 Mar 26;17(1):24. doi: 10.1038/s41368-025-00353-z.
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Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair.在脱细胞骨基质(DBM)构建体中,骨形态发生蛋白 9 刺激的人牙周韧带干细胞(hPDLSCs)的有效骨再生,用于模拟颌骨骨内缺损修复。
Stem Cell Res Ther. 2022 Dec 27;13(1):535. doi: 10.1186/s13287-022-03221-3.
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A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway.
一种新型 SATB2 突变通过 Wnt/β-catenin 信号通路抑制人牙髓干细胞的成牙本质分化。
Stem Cell Res Ther. 2021 Dec 4;12(1):595. doi: 10.1186/s13287-021-02660-8.
4
Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells.富含特殊 AT 序列结合蛋白 2(Satb2)与 Bmp9 协同作用,对于小鼠切牙间充质干细胞的成骨/成牙分化是必不可少的。
Cell Prolif. 2021 Apr;54(4):e13016. doi: 10.1111/cpr.13016. Epub 2021 Mar 4.