Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2 involvement.
Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2 involvement.
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DOI：
10.1002/stem.1544
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发表时间：
2014-01
期刊：
影响因子：
5.2
通讯作者：
Papaccio, Gianpaolo
中科院分区：
文献类型：
--
作者：
Paino, Francesca;La Noce, Marcella;Tirino, Virginia;Naddeo, Pasqualina;Desiderio, Vincenzo;Pirozzi, Giuseppe;De Rosa, Alfredo;Laino, Luigi;Altucci, Lucia;Papaccio, Gianpaolo
成人间充质干细胞，如牙髓干细胞，是非常感兴趣的细胞为基础的组织工程策略，因为它们可以分化成各种组织特异性细胞，首先是成骨细胞。近年来，干细胞的表观遗传学研究表明，特定的组蛋白改变和修饰酶在细胞分化中发挥着重要作用。然而，尽管一些研究报道了丙戊酸（VPA）-组蛋白脱乙酰酶（HDAC）的选择性抑制剂-增强成骨细胞分化，骨钙素表达的数据-分化的晚期标志物-是有限的。因此，我们决定研究VPA对牙髓干细胞分化的影响。低浓度的VPA不会降低细胞活力、增殖或细胞周期特征。然而，通过增加骨桥蛋白和骨唾液酸蛋白的表达足以显著增强基质矿化。相反，骨钙素水平降低，在转录水平诱导的效果，并与HDAC 2的抑制强烈相关。事实上，用shRNA沉默HDAC 2对成骨细胞相关标志物的表达产生了与VPA处理相似的影响。我们的结论是，丙戊酸钠不诱导终末分化的成骨细胞，但刺激产生不太成熟的细胞。此外，通过RNA干扰对单个HDAC的特异性抑制只能增强成骨细胞分化的单个方面，从而产生选择性效应。
Adult mesenchymal stem cells, such as dental pulp stem cells, are of great interest for cell-based tissue engineering strategies because they can differentiate into a variety of tissue-specific cells, above all, into osteoblasts. In recent years, epigenetic studies on stem cells have indicated that specific histone alterations and modifying enzymes play essential roles in cell differentiation. However, although several studies have reported that valproic acid (VPA)—a selective inhibitor of histone deacetylases (HDAC)—enhances osteoblast differentiation, data on osteocalcin expression—a late-stage marker of differentiation—are limited. We therefore decided to study the effect of VPA on dental pulp stem cell differentiation. A low concentration of VPA did not reduce cell viability, proliferation, or cell cycle profile. However, it was sufficient to significantly enhance matrix mineralization by increasing osteopontin and bone sialoprotein expression. In contrast, osteocalcin levels were decreased, an effect induced at the transcriptional level, and were strongly correlated with inhibition of HDAC2. In fact, HDAC2 silencing with shRNA produced a similar effect to that of VPA treatment on the expression of osteoblast-related markers. We conclude that VPA does not induce terminal differentiation of osteoblasts, but stimulates the generation of less mature cells. Moreover, specific suppression of an individual HDAC by RNA interference could enhance only a single aspect of osteoblast differentiation, and thus produce selective effects.
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影响因子：
3.3
作者：
HUI, Z;YUE, X;BEACH, D
通讯作者：
BEACH, D
DOI：
10.1016/j.bbrc.2005.05.097
发表时间：
2005-07-22
影响因子：
3.1
作者：
Hausser, HJ;Brenner, RE
通讯作者：
Brenner, RE
影响因子：
12.4
作者：
d'Aquino, R.;Graziano, A.;Papaccio, G.
通讯作者：
Papaccio, G.
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.4
作者：
Krämer, OH;Zhu, P;Göttlicher, M
通讯作者：
Göttlicher, M