TGFβ inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton.
TGFβ inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton.
复制标题
DOI：
10.1002/jbmr.2142
复制
发表时间：
2014
影响因子：
6.2
通讯作者：
Subramaniam, Malayannan
中科院分区：
文献类型：
--
作者：
Hawse, John R.;Pitel, Kevin S.;Cicek, Muzaffer;Philbrick, Kenneth A.;Gingery, Anne;Peters, Kenneth D.;Syed, Farhan A.;Ingle, James N.;Suman, Vera J.;Iwaniec, Urszula T.;Turner, Russell T.;Spelsberg, Thomas C.;Subramaniam, Malayannan
关键词：
TGFβ诱导型早期基因-1（TIEG 1）敲除（KO）小鼠表现出性别特异性骨质减少表型，其特征为雌性小鼠的骨密度、骨矿物质含量低和骨强度总体损失。因此，我们推测TIEG 1表达的缺失会损害雌激素对雌性小鼠骨的作用。为了验证这一假设，我们采用卵巢切除术（OVX）和雌激素替代模型系统，全面分析TIEG 1在组织，细胞和生化水平上介导的雌激素信号在骨中的作用。DXA，pQCT和micro-CT分析显示，TIEG 1表达的缺失降低了整个骨骼和多个骨隔室中雌激素的作用。雌激素暴露还导致野生型小鼠的骨形成率和矿化周长降低，对TIEG 1 KO小鼠的这些参数几乎没有影响。与野生型同窝小鼠相比，TIEG 1 KO小鼠雌激素治疗后，破骨细胞周长/骨周长和骨吸收活性（通过CTX-1血清水平测定）受到差异性调节。在野生型和TIEG 1 KO小鼠之间未检测到P1 NP血清水平的显著差异。总之，这些数据暗示了TIEG 1在介导整个小鼠骨骼的雌激素信号传导中的重要作用，并表明该途径中的缺陷可能导致在雌性TIEG 1 KO小鼠中观察到的性别特异性骨质减少表型。
TGFβ Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a gender specific osteopenic phenotype characterized by low bone mineral density, bone mineral content and overall loss of bone strength in female mice. We therefore speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. In order to test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell and biochemical level. DXA, pQCT and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter, and resorptive activity as determined by serum levels of CTX-1, were differentially regulated following estrogen treatment in TIEG1 KO mice compared to wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the gender specific osteopenic phenotype observed in female TIEG1 KO mice.
登录
查看更多内容
影响因子：
--
作者：
Haddad O;Hawse JR;Subramaniam M;Spelsberg TC;Bensamoun SF
通讯作者：
Bensamoun SF
影响因子：
4.1
作者：
Bensamoun, Sabine F.;Hawse, John R.;Spelsberg, Thomas C.
通讯作者：
Spelsberg, Thomas C.
影响因子：
4
作者：
Johnsen, SA;Subramaniam, M;Spelsberg, TC
通讯作者：
Spelsberg, TC
影响因子：
6.2
作者：
Hannon, R;Blumsohn, A;Eastell, R
通讯作者：
Eastell, R
影响因子：
3.5
作者：
Chalaux, E;López-Rovira, T;Ventura, F
通讯作者：
Ventura, F