Researcher, Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Undergraduate Student, College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea.
Implant Dent. 2018 Feb;27(1):33-42. doi: 10.1097/ID.0000000000000711.
Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to affect cell growth and differentiation in various in vitro and in vivo models. The aim of this study is to evaluate the effects of VPA on viability and osteogenic differentiation of mesenchymal stem cells derived from the human gingival tissue.
Stem cells derived from the gingiva were grown in the presence of VPA at concentrations ranging from 0.125 to 8 mM. Cell morphology was assessed on days 3, 5, and 7, and cell proliferation was analyzed on the same days using a Cell Counting Kit-8 (CCK-8). Alizarin Red-S staining was used to assess differentiation of the stem cells.
The control group showed a normal fibroblast morphology when cultured in growth media. The shape of cells in the 8 mM group was more flat than cells in other groups, and fewer cells were present. A statistically significant decrease in cell proliferation was seen in the 8 mM group. Results of Alizarin Red-S staining showed a significant decrease in mineralization in the 8 mM group.
Taken together, this study demonstrated that VPA, at the tested concentrations, decreases the viability of stem cells derived from the human gingiva. The decreases in osteogenic differentiation were achieved via the decrease of Rux2 expression. The concentration and application time of VPA treatment should be meticulously controlled to minimize any detrimental effects.
丙戊酸（VPA）是一种组蛋白去乙酰化酶抑制剂，已被证明可影响各种体外和体内模型中的细胞生长和分化。本研究旨在评估 VPA 对人牙龈组织来源间充质干细胞活力和成骨分化的影响。
将来自牙龈的干细胞在 0.125 至 8mM 的 VPA 浓度下培养。在第 3、5 和 7 天评估细胞形态，并用细胞计数试剂盒-8（CCK-8）分析相同天的细胞增殖。用茜素红 S 染色来评估干细胞的分化。
在生长培养基中培养时，对照组显示出正常的成纤维细胞形态。8mM 组细胞的形状比其他组更扁平，细胞数量更少。在 8mM 组中观察到细胞增殖的统计学显著下降。茜素红 S 染色的结果表明，8mM 组的矿化明显减少。
综上所述，本研究表明，在所测试的浓度下，VPA 降低了来自人牙龈的干细胞的活力。通过降低 Rux2 表达来实现成骨分化的减少。VPA 处理的浓度和应用时间应仔细控制，以尽量减少任何有害影响。
