Role of calcium-phosphate deposition in vascular smooth muscle cell calcification

Role of calcium-phosphate deposition in vascular smooth muscle cell calcification
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DOI:
10.1152/ajpcell.00229.2010
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发表时间:
2011-01-01
影响因子:
5.5
通讯作者:
Sorribas, Victor
Sorribas, Victor
中科院分区:
生物学2区
文献类型:
--
作者:
Villa-Bellosta, Ricardo;Millan, Angel;Sorribas, Victor

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Villa-Bellosta R,Millan A,Sorribas V.钙-磷酸盐沉积在血管平滑肌细胞钙化中的作用。美国生理学杂志细胞生理学300:C210-C220,2011年。首次发表于2010年9月29日; doi:10.1152/ajpcell.00229.2010。在这项工作中,我们正在研究是否磷酸钙沉积(CPD)在血管钙化是一个被动的或细胞介导的机制。在固定的血管平滑肌细胞(VSMC)中研究了被动CPD,在1.8mM Ca 2+和2 mM Pi的存在下,VSMC比活细胞钙化更快。CPD似乎是一个不依赖于细胞的过程,它取决于钙、磷酸盐和羟离子的浓度,但不取决于Ca x Pi浓度产物,因为沉积是用2 x 2和4 x 1 Ca x Pi mM(2)获得的,但不是用2 x 1或1 x 4 Ca x Pi mM(2)。用4 mM Pi孵育而不含CPD(即,加1 mM Ca)不诱导成骨细胞表达。骨标记物如Bmp 2和Cbfa 1的表达增加仅与CPD同时观察到。羟基磷灰石是裂解细胞和活细胞中唯一的结晶相。溶解的细胞沉积物是高度结晶的,而活细胞沉积物仍然含有大量的无定形钙。高分辨率透射电子显微镜揭示了在裂解细胞中随机取向的5-10 nm的圆形微晶的纳米结构,这与自发沉淀相容。活细胞中的纳米结构由10 nm厚的长纤维晶体组成,嵌入无定形基质中。这种结构表明细胞在羟基磷灰石结晶过程中的积极作用。总之,我们的数据表明CPD是一种被动现象,它触发了成骨变化,这些变化参与了组织良好的钙化晶体结构的形成。
Villa-Bellosta R, Millan A, Sorribas V. Role of calcium-phosphate deposition in vascular smooth muscle cell calcification. Am J Physiol Cell Physiol 300: C210-C220, 2011. First published September 29, 2010; doi: 10.1152/ajpcell.00229.2010.-In this work we are studying whether calcium phosphate deposition (CPD) during vascular calcification is a passive or a cell-mediated mechanism. Passive CPD was studied in fixed vascular smooth muscle cells (VSMC), which calcify faster than live cells in the presence of 1.8 mM Ca2+ and 2 mM P-i. CPD seems to be a cell-independent process that depends on the concentration of calcium, phosphate, and hydroxyl ions, but not on Ca x Pi concentration products, given that deposition is obtained with 2 x 2 and 4 x 1 Ca x Pi mM(2) but not with 2 x 1 or 1 x 4 Ca x Pi mM(2). Incubation with 4 mM Pi without CPD (i.e., plus 1 mM Ca) does not induce osteogene expression. Increased expression of bone markers such as Bmp2 and Cbfa1 is only observed concomitantly with CPD. Hydroxyapatite is the only crystalline phase in both lysed and live cells. Lysed cell deposits are highly crystalline, whereas live cell deposits still contain large amounts of amorphous calcium. High-resolution transmission electron microscopy revealed a nanostructure of rounded crystallites of 5-10 nm oriented at random in lysed cells, which is compatible with spontaneous precipitation. The nanostructure in live cells consisted of long fiber crystals, 10-nm thick, embedded in an amorphous matrix. This structure indicates an active role of cells in the process of hydroxyapatite crystallization. In conclusion, our data suggest that CPD is a passive phenomenon, which triggers the osteogenic changes that are involved in the formation of a well organized, calcified crystalline structure.