Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures
Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures
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DOI：
10.1007/s00441-005-1115-7
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发表时间：
2005-09-01
影响因子：
3.6
通讯作者：
Guicheux, J
中科院分区：
文献类型：
--
作者：
Alliot-Licht, B;Bluteau, G;Guicheux, J
再生牙髓策略需要鉴定出能够分化成牙母细胞样细胞的前体，这些细胞在损伤后分泌修复性牙本质。周细胞具有产生成骨细胞、软骨细胞和脂肪细胞的能力，这一特征导致人们认为成牙细胞样细胞可能来源于这些血管周围细胞。为了获得这一假说的新见解，我们研究了地塞米松（Dex）的作用，地塞米松是一种用于体外诱导成骨分化的合成糖皮质激素，在先前报道的含有周细胞的人牙髓培养模型中，通过其平滑肌肌动蛋白（SMA）的表达及其特定的超微结构形态来鉴定。我们的数据表明，Dex （10(-8) M）显著抑制细胞增殖，显著降低sma阳性细胞比例。相反，Dex强烈刺激碱性磷酸酶（ALP）活性，诱导编码成牙本质唾液磷酸蛋白的转录物表达。然而，甲状旁腺激素/甲状旁腺激素相关肽受体、核心结合因子a1/osf2、骨连接素和脂蛋白脂肪酶mRNA水平未被右美托酮治疗改变。Dex还增加了表达STRO-1的细胞比例，STRO-1是多电位间充质祖细胞的标记物。这些观察结果表明，糖皮质激素调节来自牙髓细胞的祖细胞形成成牙细胞样细胞的承诺，同时减少sma阳性细胞的比例。这些结果为解释修复性牙本质形成的细胞和分子机制提供了新的视角。
Regenerative dental pulp strategies require the identification of precursors able to differentiate into odontoblast-like cells that secrete reparative dentin after injury. Pericytes have the ability to give rise to osteoblasts, chondrocytes, and adipocytes, a feature that has led to the suggestion that odontoblast-like cells could derive from these perivascular cells. In order to gain new insights into this hypothesis, we investigated the effects of dexamethasone (Dex), a synthetic glucocorticoid employed to induce osteogenic differentiation in vitro, in a previously reported model of human dental pulp cultures containing pericytes as identified by their expression of smooth muscle actin (SMA) and their specific ultrastructural morphology. Our data indicated that Dex (10(-8) M) significantly inhibited cell proliferation and markedly reduced the proportion of SMA-positive cells. Conversely, Dex strongly stimulated alkaline phosphatase (ALP) activity and induced the expression of the transcript encoding the major odontoblastic marker, dentin sialophosphoprotein. Nevertheless, parathyroid hormone/parathyroid hormone-related peptide receptor, core-binding factor a1/osf2, osteonectin, and lipoprotein lipase mRNA levels were not modified by Dex treatment. Dex also increased the proportion of cells expressing STRO-1, a marker of multipotential mesenchymal progenitor cells. These observations indicate that glucocorticoids regulate the commitment of progenitors derived from dental pulp cells to form odontoblast-like cells, while reducing the proportion of SMA-positive cells. These results provide new perspectives in deciphering the cellular and molecular mechanisms leading to reparative dentinogenesis.