Impaired osteoblast differentiation in annexin A2- and -A5-deficient cells.
Impaired osteoblast differentiation in annexin A2- and -A5-deficient cells.
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膜联蛋白A2和-A5缺陷细胞中成骨细胞分化受损。
DOI：
10.1371/journal.pone.0107482
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yellowley CE
中科院分区：
文献类型：
--
作者：
Genetos DC;Wong A;Weber TJ;Karin NJ;Yellowley CE
膜联蛋白是一类钙离子结合蛋白，在调节脂筏、炎症、纤溶、转录编程和离子转运等方面具有多种功能。在骨内，它们被很好地表征为矿化基质囊泡的组分，尽管很少有人知道它们在骨生成过程中的功能。我们使用shRNA产生膜联蛋白A2（AnxA 2）-或膜联蛋白A5（AnxA 5）-敲低的前成骨细胞，并确定与pSiren（Si）对照相比，在敲低的细胞中增殖或成骨分化是否改变。我们报告说，DNA含量，增殖的标志物，显着减少AnxA 2和AnxA 5敲低细胞。碱性磷酸酶的表达和活性也被抑制在AnxA 2-或AnxA 5-敲低培养14天后。与pSiren相比，在敲除细胞中成骨基因表达的模式发生了改变，Col 1a 1在敲除细胞中表达更快。相反，Runx 2、Ibsp和Bglap在培养14天后均显示表达降低。在AnxA 2和AnxA 5敲低中，与pSiren对照相比，白细胞介素诱导的STAT 6信号传导显著减弱。这些数据表明，AnxA 2和AnxA 5可以通过调节骨祖细胞增殖，分化和细胞因子的反应性来影响骨形成，除了它们在基质囊泡中的功能。
Annexins are a class of calcium-binding proteins with diverse functions in the regulation of lipid rafts, inflammation, fibrinolysis, transcriptional programming and ion transport. Within bone, they are well-characterized as components of mineralizing matrix vesicles, although little else is known as to their function during osteogenesis. We employed shRNA to generate annexin A2 (AnxA2)- or annexin A5 (AnxA5)-knockdown pre-osteoblasts, and determined whether proliferation or osteogenic differentiation was altered in knockdown cells, compared to pSiren (Si) controls. We report that DNA content, a marker of proliferation, was significantly reduced in both AnxA2 and AnxA5 knockdown cells. Alkaline phosphatase expression and activity were also suppressed in AnxA2- or AnxA5-knockdown after 14 days of culture. The pattern of osteogenic gene expression was altered in knockdown cells, with Col1a1 expressed more rapidly in knock-down cells, compared to pSiren. In contrast, Runx2, Ibsp, and Bglap all revealed decreased expression after 14 days of culture. In both AnxA2- and AnxA5-knockdown, interleukin-induced STAT6 signaling was markedly attenuated compared to pSiren controls. These data suggest that AnxA2 and AnxA5 can influence bone formation via regulation of osteoprogenitor proliferation, differentiation, and responsiveness to cytokines in addition to their well-studied function in matrix vesicles.
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影响因子：
2.6
作者：
Jung, Younghun;Shiozawa, Yusuke;Taichman, Russell S.
通讯作者：
Taichman, Russell S.
影响因子：
2.7
作者：
Collette, Nicole M.;Genetos, Damian C.;Murugesh, Deepa;Harland, Richard M.;Loots, Gabriela G.
通讯作者：
Loots, Gabriela G.
影响因子：
4.1
作者：
Genetos, Damian C.;Wong, Alice;Watari, Shinya;Yellowley, Clare E.
通讯作者：
Yellowley, Clare E.
影响因子：
4
作者：
Genetos, Damian C.;Toupadakis, Chrisoula A.;Raheja, Leah F.;Wong, Alice;Papanicolaou, Savvas E.;Fyhrie, David P.;Loots, Gabriela G.;Yellowley, Clare E.
通讯作者：
Yellowley, Clare E.
影响因子：
4
作者：
Gillette, JM;Nielsen-Preiss, SM
通讯作者：
Nielsen-Preiss, SM