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.
Cell Prolif. 2021 Apr;54(4):e13016. doi: 10.1111/cpr.13016. Epub 2021 Mar 4.
Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs.
Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo.
Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo.
Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.
小鼠切牙间充质干细胞（MSCs）具有自我更新能力和骨/牙向分化潜能。然而，控制小鼠切牙 MSCs 持续自我更新和骨/牙向分化的机制尚不清楚。特殊富含 AT 的序列结合蛋白 2（SATB2）正向调节颅面模式形成、骨发育和再生，而 SATB2 缺失或突变导致颅面骨发育不良和牙齿及牙根发育迟缓，类似于骨形态发生蛋白（BMP）功能丧失表型。然而，SATB2 在牙源性 MSCs 中的作用的详细机制尚不清楚。本研究旨在探讨 SATB2 是否可以调节牙源性 MSCs 的自我更新和骨/牙向分化。
通过免疫荧光染色、定量 RT-PCR 和 Western blot 分析检测快速更新的小鼠切牙间质中 Satb2 的表达。构建 Ad-Satb2 和 Ad-siSatb2，以评估 Satb2 对牙源性 MSCs 自我更新和骨/牙向分化特性的影响，以及 Satb2 与成骨因子骨形态发生蛋白 9（Bmp9）在体外和体内的潜在作用。
发现 Satb2 在间充质细胞和前期成牙本质细胞/成牙本质细胞中表达。我们进一步发现 Satb2 有效地增强了小鼠切牙 MSCs 的自我更新。Satb2 与强骨形成因子 Bmp9 协同作用，在体外和体内诱导小鼠切牙 MSCs 的骨/牙向分化。
Satb2 促进小鼠切牙 MSCs 的自我更新和骨/牙向分化。因此，Satb2 可以与 Bmp9 合作，作为成骨再生和牙齿工程的新有效生物因子。
