Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries.
Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries.
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DOI：
10.1161/circresaha.108.183053
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发表时间：
2009-03-27
影响因子：
20.1
通讯作者：
Giachelli CM
中科院分区：
文献类型：
--
作者：
Speer MY;Yang HY;Brabb T;Leaf E;Look A;Lin WL;Frutkin A;Dichek D;Giachelli CM
血管钙化是心血管疾病发病率和死亡率的主要危险因素。为了制定合适的预防和/或治疗血管钙化的策略，了解参与这一过程的细胞的来源是很重要的。在这份报告中，我们使用SM22-Cre重组酶和rosa26-LacZ等位基因对来源于平滑肌的细胞进行遗传示踪。我们发现在基质-Gla蛋白缺陷(Mgp-−/−)小鼠的钙化血管中，平滑肌细胞(SMC)可分化为骨软骨前体细胞和软骨细胞样细胞。SMC的这种谱系重新编程发生在钙沉积之前，并与Runx2/Cbfa1表达的早期开始以及Myocardin和MSX2的下调有关。Sox9和BMP2的组成性表达没有变化。钙化的MGP−/−和非钙化的野生型(MGP+/+)血管均未检测到Osterix、WNT3a和WNT7a的mRNAs。最后，体外机制研究表明，在钙化条件下，ERK信号可能是SMC转分化所必需的。这些结果有力地支持了成人SMC可以转分化的假说，SMC转分化是导致血管钙化和钙化血管病变中骨骼元素出现的重要过程。
Vascular calcification is a major risk factor for cardiovascular morbidity and mortality. In order to develop appropriate prevention and/or therapeutic strategies for vascular calcification, it is important to understand the origins of the cells that participate in this process. In this report, we used the SM22-Cre recombinase and Rosa26-LacZ alleles to genetically trace cells derived from smooth muscle. We found that smooth muscle cells (SMCs) gave rise to osteochondrogenic precursor- and chondrocyte-like cells in calcified blood vessels of matrix Gla protein deficient (MGP−/−) mice. This lineage reprogramming of SMCs occurred prior to calcium deposition, and was associated with an early onset of Runx2/Cbfa1 expression and the down regulation of myocardin and Msx2. There was no change in the constitutive expression of Sox9 or BMP2. Osterix, Wnt3a and Wnt7a mRNAs were not detected in either calcified MGP−/− or non-calcified wild type (MGP+/+) vessels. Finally, mechanistic studies in vitro suggest that Erk signaling might be required for SMC transdifferentiation under calcifying conditions. These results provide strong support for the hypothesis that adult SMCs can transdifferentiate and that SMC transdifferentiation is an important process driving vascular calcification and the appearance of skeletal elements in calcified vascular lesions.