The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells.
The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells.
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DOI：
10.1371/journal.pone.0019595
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
MacRae VE
中科院分区：
文献类型：
--
作者：
Zhu D;Mackenzie NC;Millán JL;Farquharson C;MacRae VE
血管钙化是心血管风险升高的指标。血管平滑肌细胞（VSMC）是参与内侧血管钙化的主要细胞类型，可以在钙化环境中经历向成骨细胞和软骨细胞细胞的表型转变。在本研究中，通过体外 VSMC 钙化研究与小鼠内侧钙化模型的离体分析，我们发现血管钙化也与骨细胞表型标记物的表达相关。作为对照，在钙化介质（含有β-甘油磷酸和抗坏血酸）存在的情况下体外诱导小鼠颅骨成骨细胞最终分化为骨细胞，通过骨细胞标记物 DMP-1、E11 和硬化蛋白的表达增加来确定。在相同条件下培养小鼠主动脉 VSMC 证实，这些细胞的钙化也可以在类似的钙化介质中诱导。钙化的 VSMC 碱性磷酸酶活性和 PiT-1 表达增加，这是公认的血管钙化标志物。体外 VSMC 钙化过程中 DMP-1、E11 和硬化蛋白的表达上调。在 Enpp1−/− 小鼠主动脉组织的钙化介质中还观察到由更成熟的骨细胞表达的 E11（一种早期骨细胞标记物）和硬化蛋白的蛋白质表达增加。这项研究证明了血管钙化过程中关键骨细胞分子的上调。更全面地了解骨细胞形成的功能作用，特别是硬化素和 E11 在血管钙化过程中的表达，可能会为临床干预确定新的潜在治疗策略。
Vascular calcification is an indicator of elevated cardiovascular risk. Vascular smooth muscle cells (VSMCs), the predominant cell type involved in medial vascular calcification, can undergo phenotypic transition to both osteoblastic and chondrocytic cells within a calcifying environment. In the present study, using in vitro VSMC calcification studies in conjunction with ex vivo analyses of a mouse model of medial calcification, we show that vascular calcification is also associated with the expression of osteocyte phenotype markers. As controls, the terminal differentiation of murine calvarial osteoblasts into osteocytes was induced in vitro in the presence of calcifying medium (containing ß-glycerophosphate and ascorbic acid), as determined by increased expression of the osteocyte markers DMP-1, E11 and sclerostin. Culture of murine aortic VSMCs under identical conditions confirmed that the calcification of these cells can also be induced in similar calcifying medium. Calcified VSMCs had increased alkaline phosphatase activity and PiT-1 expression, which are recognized markers of vascular calcification. Expression of DMP-1, E11 and sclerostin was up-regulated during VSMC calcification in vitro. Increased protein expression of E11, an early osteocyte marker, and sclerostin, expressed by more mature osteocytes was also observed in the calcified media of Enpp1−/− mouse aortic tissue. This study has demonstrated the up-regulation of key osteocytic molecules during the vascular calcification process. A fuller understanding of the functional role of osteocyte formation and specifically sclerostin and E11 expression in the vascular calcification process may identify novel potential therapeutic strategies for clinical intervention.
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影响因子：
4.1
作者：
MacRae, Vicky E.;Davey, Megan G.;Farquharson, Colin
通讯作者：
Farquharson, Colin
影响因子：
20.1
作者：
Li, XW;Yang, HY;Giachelli, CM
通讯作者：
Giachelli, CM
影响因子：
6.2
作者：
Li, Xiaodong;Ominsky, Michael S.;Paszty, Chris
通讯作者：
Paszty, Chris
影响因子：
4.1
作者：
Aarden, EM;Nijweide, PJ;Helfrich, MH
通讯作者：
Helfrich, MH
DOI：
10.1074/mcp.m110.001693
发表时间：
2010-09
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Didangelos A;Yin X;Mandal K;Baumert M;Jahangiri M;Mayr M
通讯作者：
Mayr M