TGFβ inducible early gene-1 knockout mice display defects in bone strength and microarchitecture

TGFβ inducible early gene-1 knockout mice display defects in bone strength and microarchitecture
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DOI:
10.1016/j.bone.2006.05.021
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发表时间:
2006-12-01
期刊:
影响因子:
4.1
通讯作者:
Spelsberg, Thomas C.
Spelsberg, Thomas C.
中科院分区:
医学2区
文献类型:
--
作者:
Bensamoun, Sabine F.;Hawse, John R.;Spelsberg, Thomas C.

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转化生长因子β诱导早期基因-1(TIEG)是最初从人成骨细胞中克隆的Sp/Kruppel样转录因子家族的成员。我们先前已经证明,TIEG在重要的成骨细胞标志基因的表达和成骨细胞的成熟/分化中发挥作用。为了阐明TIEG在骨骼发育和维持中的作用,我们培育了一只TIEG基因敲除(KO)小鼠。三点弯曲试验表明,TIEG KO小鼠的股骨明显弱于野生型动物。对胫骨的pQCT分析显示,与野生型小鼠相比,KO动物的骨含量、密度和大小显著降低。对股骨头和椎骨的Micro-CT分析显示,与野生型对照组相比,KO组小鼠的股骨头小梁间隔增加,皮质骨厚度和椎骨体积减少。此外,电子显微镜显示KO小鼠股骨中的骨细胞数量显著减少。综上所述,这些数据表明,TIEG KO小鼠的骨骼表现出明显的骨质疏松表型,骨骼明显变弱,皮质和松质骨数量减少。综上所述,TIEG在骨骼发育和/或动态平衡中发挥着重要作用。(C)2006 Elsevier Inc.保留所有权利。
TGF beta inducible early gene-1 (TIEG) is a member of the Sp/Kruppel-like transcription factor family originally cloned from human osteoblasts. We have previously demonstrated that TIEG plays a role in the expression of important osteoblast marker genes and in the maturation/differentiation of osteoblasts. To elucidate the function of TIEG in skeletal development and maintenance, we have generated a TIEG knockout (KO) mouse. Three-point bending tests demonstrated that the femurs of TIEG KO mice are significantly weaker than those of wild-type animals. pQCT analysis of tibias revealed significant decreases in bone content, density and size in KO animals compared to wild-type mice. Micro-CT analysis of the femoral head and vertebrae revealed increases in femoral head trabecular separation and decreases in cortical bone thickness and vertebral bone volume in KO mice relative to wild-type controls. In addition, electron microscopy indicated a significant decrease in osteocyte number in the femurs of KO mice. Taken together, these data demonstrate that the bones of TIEG KO mice display an osteopenic phenotype with significantly weaker bones and reduced amounts of cortical and trabecular bone. In summary, an important role for TIEG in skeletal development and/or homeostasis is indicated. (c) 2006 Elsevier Inc. All rights reserved.