Hypoxia increases Annexin A2 expression in osteoblastic cells via VEGF and ERK.
Hypoxia increases Annexin A2 expression in osteoblastic cells via VEGF and ERK.
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DOI：
10.1016/j.bone.2010.08.024
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发表时间：
2010-12
期刊：
影响因子：
4.1
通讯作者：
Yellowley, Clare E.
中科院分区：
文献类型：
--
作者：
Genetos, Damian C.;Wong, Alice;Watari, Shinya;Yellowley, Clare E.
血管内皮生长因子 (VEGF) 刺激的血管生成对于骨发育和骨修复过程中发生的软骨内骨化至关重要。在这些情况下，VEGF 的产生似乎是由低氧张力驱动的，并受到转录因子缺氧诱导因子-α 家族 (HIF-α) 的控制。膜联蛋白 2 (AnxA2) 是一种钙依赖性磷脂结合蛋白，与 VEGF 介导的视网膜新生血管形成有关，并且在脉络膜视网膜内皮细胞中被 VEGF 上调。 AnxA2 也在成骨细胞谱系和软骨细胞中表达，并可能在基质矿化中发挥作用。在本文中，我们研究了缺氧（1% O2）和 VEGF 对成骨细胞 MC3T3-E1 细胞中 AnxA2 表达的影响。缺氧、去铁敏（缺氧模拟物）和重组 VEGF 均增加了成骨细胞中 AnxA2 mRNA 和蛋白质水平。缺氧诱导的 AnxA2 增加被 VEGF-R1 阻断抗体抑制，然而 VEGF120（一种 VEGF-R1 激动剂）对 Anxa2 表达没有影响。这表明 VEGF 对膜联蛋白 A2 的诱导并非单独通过 VEGF-R1 激动介导，而是通过 VEGF-R1 和 Neuropilin-1 或 Neuropilin-2 异二聚体介导。此外，我们证明 VEGF 通过涉及 Src 和 MEK 激酶的途径刺激 AnxA2 表达的变化。这些数据表明，成骨细胞中的 AnxA2 表达受到 VEGF 的控制，这可能对低氧条件下的血管生成和骨矿化具有影响。
Vascular endothelial growth factor (VEGF) stimulated angiogenesis is critical for endochondral ossification that occurs during bone development, and bone repair. Under these circumstances, VEGF production appears to be driven by low oxygen tension, under the control of the hypoxia inducible factor-α family of transcription factors (HIF-α). Annexin 2 (AnxA2) a calcium dependant phospholipid binding protein has been implicated in VEGF-mediated retinal neovascularization and is upregulated by VEGF in choroid retinal endothelial cells. AnxA2 is also expressed in cells of the osteoblast lineage and chondrocytes and may play a role in matrix mineralization. In this paper we examined the effects of hypoxia (1% O2) and VEGF on the expression of AnxA2 in osteoblastic MC3T3-E1 cells. Hypoxia, desferrioxamine (hypoxia mimetic) and recombinant VEGF all increased AnxA2 mRNA and protein levels in osteoblastic cells. The hypoxia-induced increase in AnxA2 was inhibited by a blocking antibody to VEGF-R1, however, VEGF120, a VEGF-R1 agonist demonstrated no influence upon Anxa2 expression. This suggests that VEGF induction of Annexin A2 is not mediated via VEGF-R1 agonism alone, but by VEGF-R1 and Neuropilin-1 or Neuropilin-2 heterodimers. Additionally we demonstrated that VEGF-stimulated changes in AnxA2 expression via a pathway involving Src and MEK kinase. These data demonstrate that AnxA2 expression in osteoblasts is under the control of VEGF, which may have implications for both angiogenesis and bone mineralization under low oxygen conditions.
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DOI：
10.1111/j.1748-1716.1984.tb07438.x
发表时间：
1984-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
GRONLUND, J;KOFOED, H;SVALASTOGA, E
通讯作者：
SVALASTOGA, E
影响因子：
5.6
作者：
Kanichai, Manoj;Ferguson, Damien;Campbell, Veronica A.
通讯作者：
Campbell, Veronica A.
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：
6.2
作者：
Chen, Neal X.;O'Neill, Kalisha D.;Moe, Sharon M.
通讯作者：
Moe, Sharon M.
影响因子：
11.5
作者：
Bello, L;Lucini, V;Bikfalvi, A
通讯作者：
Bikfalvi, A