Simvastatin Promotes Odontoblastic Differentiation and Expression of Angiogenic Factors via Heme Oxygenase-1 in Primary Cultured Human Dental Pulp Cells
Simvastatin Promotes Odontoblastic Differentiation and Expression of Angiogenic Factors via Heme Oxygenase-1 in Primary Cultured Human Dental Pulp Cells
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DOI：
10.1016/j.joen.2009.11.021
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发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Kim, Eun-Cheol
中科院分区：
文献类型：
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作者：
Min, Kyung-San;Lee, Young-Man;Kim, Eun-Cheol
引言：虽然辛伐他汀具有多种可证实的作用，但其在牙本质形成中的作用仍不清楚。在这项研究中，我们测试的假设，除了辛伐他汀的人牙髓细胞（HDPC）刺激牙发育，促进成牙本质细胞分化和有利于血管生成因子的释放。此外，血红素氧合酶-1（HO-1）在这些影响中的作用进行了研究。研究方法：通过碱性磷酸酶（ALP）活性、茜素红染色和Western印迹分析成牙本质细胞分化和血管生成标志物的表达。结果如下：辛伐他汀通过上调矿化结节、牙源性标记物以及血管生成标记物来增强HDPC的分化。然后将这些现象与HO-1蛋白水平的诱导相关联。辛伐他汀对成牙本质细胞分化和血管生成的诱导作用被HO-1抑制剂和一氧化碳（CO）清除剂所抵消。结论：这些结果表明，辛伐他汀通过涉及HO-1及其产物CO的作用的机制在HDPC中发挥其成牙本质细胞分化和血管生成诱导作用（J Endod 2010;36：447-452）。
Introduction: Although simvastatin has multiple demonstrable effects, its function in dentinogenesis remains unclear. In this study, we tested the hypothesis that the addition of simvastatin to human dental pulp cells (HDPCs) stimulates odontogenesis both by promoting odontoblastic differentiation and by favoring the release of angiogenic factors. In addition, the role of heme oxygenase-1 (HO-1) in these effects was investigated. Methods: The expression of markers for odontoblastic differentiation and angiogenesis was analyzed by means of alkaline phosphatase (ALP) activity, alizarin red staining, and Western blotting. Results: Simvastatin enhanced the differentiation of HDPCs by up-regulating mineralization nodules and odontogenic markers as well as angiogenic markers. These phenomena were then correlated with the induction of HO-1 protein levels. The inducing effect of simvastatin on odontoblastic differentiation and angiogenesis was nullified by an HO-1 inhibitor and a carbon monoxide (CO) scavenger. Conclusions: These results suggested that simvastatin exerts its odontoblastic differentiation and angiogenesis-inducing effects in HDPCs through a mechanism that involves the action of HO-1 and its product CO. (J Endod 2010;36:447-452)