Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo

Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo
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DOI:
10.1016/j.joen.2008.11.024
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发表时间:
2009-03-01
影响因子:
4.2
通讯作者:
Kuboki, Takuo
Kuboki, Takuo
中科院分区:
医学2区
文献类型:
--
作者:
Okamoto, Yosuke;Sonoyama, Wataru;Kuboki, Takuo

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他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂,已知可以促进骨形成。然而,他汀类药物是否影响牙髓细胞的分化尚不清楚。本研究采用细胞增殖实验、细胞周期分析、定量逆转录聚合酶链式反应(RT-PCR)和体内移植等方法,检测辛伐他汀对人牙髓干细胞(DPSCS)体外和体内的影响。1 mU/L的辛伐他汀可显著抑制DPSCs的增殖,而不诱导细胞凋亡。定量RT-PCR显示,与骨形态发生蛋白-2处理相比,辛伐他汀处理DPSCs后,骨钙素和牙本质涎磷蛋白均显著上调。体内移植数据显示,辛伐他汀治疗促进了矿化组织的形成。综上所述,他汀类药物可能是促进DPSCs分化的理想活性成分。(J Endod 2009;35:367-372)
Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mu mol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs. (J Endod 2009;35:367-372)