Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells
Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells
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DOI：
10.1161/01.atv.19.9.2112
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发表时间：
1999-09-01
影响因子：
8.7
通讯作者：
Morii, H
中科院分区：
文献类型：
--
作者：
Mori, K;Shioi, A;Morii, H
血管钙化常与动脉粥样硬化病变有关。此外，动脉粥样硬化钙化的过程具有与骨骼组织矿化相似的几个特征。因此，我们假设血管平滑肌细胞在动脉粥样硬化病变的发展过程中可能获得成骨细胞的特征。在本研究中，我们研究了地塞米松（Dex），这是众所周知的是一个有效的刺激成骨细胞分化的体外，血管钙化的影响，通过使用体外钙化模型。我们证明，地塞米松增加牛血管平滑肌细胞（BVSMC）钙化的剂量和时间依赖性的方式，地塞米松还增强了成骨细胞的几个表型标记，如碱性磷酸酶活性，前胶原I型羧基末端肽的生产，和cAMP的反应，甲状旁腺激素在BVSMC。我们还研究了Dex对人成骨细胞样（Saos-2）细胞的作用，并比较了其对BVSMCs和Saos-2细胞的作用。Dex对BVSMCs碱性磷酸酶活性和cAMP对甲状旁腺激素反应的影响不如Saos-2细胞显著。有趣的是，我们检测到Osf 2/Cbfa 1，成骨细胞分化的关键转录因子，在BVSMCs和Saos-2细胞中表达，Dex增加了这两种转录因子的基因表达。这些结果表明，Dex可以促进BVSMCs在体外的成骨分化。
Vascular calcification is often associated with atherosclerotic lesions. Moreover, the process of atherosclerotic calcification has several features similar to the mineralization of skeletal tissue. Therefore, we hypothesized that vascular smooth muscle cells might acquire osteoblastic characteristics during the development of atherosclerotic lesions. In the present study, we investigated the effect of dexamethasone (Dex), which is well known to be a potent stimulator of osteoblastic differentiation in vitro, on vascular calcification by using an in vitro calcification model. We demonstrated that Dex increased bovine vascular smooth muscle cell (BVSMC) calcification in a dose- and time-dependent manner, Dex also enhanced several phenotypic markers of osteoblasts, such as alkaline phosphatase activity, procollagen type I carboxy-terminal peptide production, and cAMP responses to parathyroid hormone in BVSMCs. We also examined the effects of Dex on human osteoblast-like (Saos-2) cells and compared its effects on BVSMCs and Saos-2 cells. The effects of Dex on alkaline phosphatase activity and the cAMP response to parathyroid hormone in BVSMCs were less prominent than those in Saos-2 cells. Interestingly, we detected that Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation, was expressed in both BVSMCs and Saos-2 cells and that Dex increased the gene expression of both transcription factors. These findings suggest that Dex may enhance osteoblastic differentiation of BVSMCs in vitro.