Wang Sainan, Mu Jinquan, Fan Zhipeng, Yu Yan, Yan Ming, Lei Gang, Tang Chunbo, Wang Zilu, Zheng Yangyu, Yu Jinhua, Zhang Guangdong
Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Stem Cell Res. 2012 May;8(3):346-56. doi: 10.1016/j.scr.2011.12.005. Epub 2011 Dec 21.
Insulin-like growth factor 1 (IGF-1) plays an important role in the regulation of tooth root development, and stem cells from apical papilla (SCAPs) are responsible for the formation of root pulp and dentin. To date, it remains unclear whether IGF-1 can regulate the function of SCAPs. In this study, SCAPs were isolated and purified from human immature root apex, and stimulated by 100 ng/mL exogenous IGF-1. The effects of IGF-1 on the proliferation and differentiation of SCAPs were subsequently investigated. IGF-1 treated SCAPs presented the morphological and ultrastructural changes. Cell proliferation, alkaline phosphatase (ALP) activity and mineralization capacity of SCAPs were increased by IGF-1. Western blot and quantitative RT-PCR analyses further demonstrated that the expression of osteogenic-related proteins and genes (e.g., alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin) was significantly up-regulated in IGF-1 treated SCAPs, whereas the expression of odontoblast-specific markers (e.g., dentin sialoprotein and dentin sialophosphoprotein) was down-regulated by IGF-1. In vivo results revealed that IGF-1 treated SCAPs mostly gave birth to bone-like tissues while untreated SCAPs mainly generated dentin-pulp complex-like structures after transplantation. The present study revealed that IGF-1 can promote the osteogenic differentiation and osteogenesis capacity of SCAPs, but weaken their odontogenic differentiation and dentinogenesis capability, indicating that IGF-1 treated SCAPs can be used as a potential candidate for bone tissue engineering.
胰岛素样生长因子1(IGF-1)在牙根发育的调节中起重要作用,而根尖乳头干细胞(SCAPs)负责牙髓和牙本质的形成。迄今为止,IGF-1是否能调节SCAPs的功能仍不清楚。在本研究中,从人未成熟根尖分离并纯化SCAPs,并用100 ng/mL外源性IGF-1进行刺激。随后研究了IGF-1对SCAPs增殖和分化的影响。IGF-1处理的SCAPs呈现出形态和超微结构的变化。IGF-1增加了SCAPs的细胞增殖、碱性磷酸酶(ALP)活性和矿化能力。蛋白质免疫印迹法和定量逆转录-聚合酶链反应分析进一步表明,在IGF-1处理的SCAPs中,成骨相关蛋白和基因(如碱性磷酸酶、 runt相关转录因子2、osterix和骨钙素)的表达显著上调,而IGF-1下调了成牙本质细胞特异性标志物(如牙本质涎蛋白和牙本质涎磷蛋白)的表达。体内结果显示,移植后,IGF-1处理的SCAPs大多形成类骨组织,而未处理的SCAPs主要形成牙本质-牙髓复合体样结构。本研究表明,IGF-1可促进SCAPs的成骨分化和成骨能力,但减弱其成牙分化和牙本质形成能力,这表明IGF-1处理的SCAPs可作为骨组织工程的潜在候选细胞。