Hypoxia suppresses Runx2 independent of modeled microgravity
Hypoxia suppresses Runx2 independent of modeled microgravity
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DOI：
10.1002/jcp.20054
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发表时间：
2004-08-01
影响因子：
5.6
通讯作者：
McCabe, LR
中科院分区：
文献类型：
--
作者：
Ontiveros, C;Irwin, R;McCabe, LR
骨骼丢失是骨骼卸载的结果，就像在卧位太空飞行中看到的那样。卸载会减少骨骼中的氧合作用和成骨细胞的分化/功能。此前，我们通过在水平旋转壁血管(RWV)中培养分化的小鼠成骨细胞，在体外模拟卸载，结果抑制了成骨细胞分化的主要转录调节因子Runx2的表达。然而，RWV能够以受控的方式再现至少两个直接相关的废弃方面，即模型微重力和低氧。RWV的缺氧表现为中氧分压降低和GAPDH和VEGF表达增加。为了分离模型微重力和低氧在抑制Runx2表达中的作用，我们在模型微重力(充氧，水平RWV旋转)、低氧(垂直RWV旋转)或两种条件(水平RWV旋转)下培养成骨细胞。Runx2的表达、DNA结合活性和启动子活性在低氧而不是常氧模拟微重力RWV条件下受到抑制。与低氧在抑制Runx2中的作用一致，直接暴露于低氧本身就足以抑制生长在标准组织培养板中的成骨细胞中Runx2的表达。综上所述，我们的研究结果表明，与骨骼卸载相关的低氧可能是Runx2表达的主要抑制因子，导致成骨细胞分化和骨形成受到抑制。(C)2004年Wiley-Liss公司
Bone loss is a consequence of skeletal unloading as seen in bed restand space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation. However, the RWV is able to reproduce in a controlled fashion at least two aspects of disuse that are directly linked, model microgravity and hypoxia. Hypoxia in the RWV is indicated by reduced medium oxygen tension and increased expression of GAPDH and VEGF. TO uncouple the role of model microgravity from hypoxia in suppressed runx2 expression, we Cultured osteoblasts under modeled microgravity (oxygenated, horizontal RWV rotation), hypoxia (vertical RWV rotation), or both conditions (horizontal RWV rotation). The expression, DNA binding activity and promoter activity of runx2, was suppressed under hypoxic but not normoxic modeled microgravity RWV conditions. Consistent with a role for hypoxia in suppression of runx2, direct exposure to hypoxia alone is Sufficient to suppress runx2 expression in osteoblasts grown in standard tissue culture plates. Taken together, our findings indicate that hypoxia associated with skeletal unloading could be major suppressor of runx2 expression leading to Suppressed osteoblast differentiation and bone formation. (C) 2004 Wiley-Liss, Inc.