TIEG-null mice display an osteopenic gender-specific phenotype
TIEG-null mice display an osteopenic gender-specific phenotype
复制标题
DOI：
10.1016/j.bone.2008.02.004
复制
发表时间：
2008-06-01
期刊：
影响因子：
4.1
通讯作者：
Subramaniam, M.
中科院分区：
文献类型：
--
作者：
Hawse, J. R.;Iwaniec, U. T.;Subramaniam, M.
TGF β诱导型早期基因-1（TIEG）最初是从人成骨细胞（OB）中克隆的，并已被证明在TGF β/Smad信号传导、基因表达调控以及OB生长和分化中发挥重要作用。为了更好地理解TIEG在骨骼中的生物学作用，我们在纯C57 BL/6背景中产生了同源TIEG-无效（TIEG（-/-））小鼠。通过使用DXA和pQCT分析，我们已经证明了两个月大的雌性TIEG（-/-）小鼠的股骨和胫骨相对于野生型（WT）同窝小鼠显示出总骨矿物质含量、密度和面积的显著降低。然而，在雄性小鼠中未观察到任何这些骨参数的差异。雌性TIEG（-/-）小鼠骨表型的进一步表征涉及机械3点弯曲试验、显微CT和骨的组织形态计量学分析。3点弯曲试验显示，与WT同窝小鼠相比，雌性TIEG（-/-）小鼠的股骨强度降低，柔韧性增加。对两个月大雌性TIEG（-/-）小鼠股骨的微型CT分析显示，与WT同窝小鼠相比，皮质骨参数显着降低。股骨远端的组织形态学评价显示，雌性TIEG（-/-）小鼠的松质骨面积也减少了31%，这主要是由于小梁数量减少。在细胞水平，雌性TIEG（-/-）小鼠表现出骨形成率降低42%，这几乎完全是由于双标记周长的减少。WT和TIEG（-/-）小鼠之间未检测到矿物质沉积率的差异。总之，这些发现表明雌性TIEG（-/-）小鼠骨质减少主要是由于功能性/成熟OB的总数减少。All rights reserved.
TGF beta inducible early gene-1 (TIEG) was originally cloned from human osteoblasts (OB) and has been shown to play an important role in TGF beta/Smad signaling, regulation of gene expression and OB growth and differentiation. To better understand the biological role of TIEG in the skeleton, we have generated congenic TIEG-null (TIEG(-/-)) mice in a pure C57BL/6 background. Through the use of DXA and pQCT analysis, we have demonstrated that the femurs and tibias of two-month-old female TIEG(-/-) mice display significant decreases in total bone mineral content, density, and area relative to wild-type (WT) littermates. However, no differences were observed for any of these bone parameters in male mice. Further characterization of the bone phenotype of female TIEG(-/-) mice involved mechanical 3-point bending tests, micro-CT, and histomorphometric analyses of bone. The 3-point bending tests revealed that the femurs of female TIEG(-/-) mice have reduced strength with increased flexibility compared to WT littermates. Micro-CT analysis of femurs of two-month-old female TIEG(-/-) mice revealed significant decreases in cortical bone parameters compared to WT littermates. Histomorphometric evaluation of the distal femur revealed that female TIEG(-/-) mice also display a 31% decrease in cancellous bone area, which is primarily due to a decrease in trabecular number. At the cellular level, female TIEG(-/-) mice exhibit a 42% reduction in bone formation rate which is almost entirely due to a reduction in double labeled perimeter. Differences in mineral apposition rate were not detected between WT and TIEG(-/-) mice. Taken together, these findings suggest that female TIEG(-/-) mice are osteopenic mainly due to a decrease in the total number of functional/mature OBs. (C) 2008 Elsevier Inc. All rights reserved.