Estrogen regulation of apoptosis in osteoblasts.
Estrogen regulation of apoptosis in osteoblasts.
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DOI：
10.1016/j.physbeh.2009.04.025
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发表时间：
2010-02-09
影响因子：
2.9
通讯作者：
Chrzan, Brian G.
中科院分区：
文献类型：
--
作者：
Bradford, Peter G.;Gerace, Ken V.;Roland, Renee L.;Chrzan, Brian G.
细胞凋亡失调是与骨质疏松等退行性疾病相关的重要疾病。在骨中，雌激素缺乏与成骨细胞凋亡加速和骨质疏松性骨折易感性有关。激素治疗仍然是预防骨质疏松症和骨折的有效选择。暴露于依托opo苷或炎性细胞因子TNFα诱导G-292人成骨细胞凋亡可促进急性caspase-3/7活性，而雌二醇预处理可抑制这种活性的增加。依托泊苷还增加了一系列促凋亡基因的表达，而这种表达也被雌二醇抑制。在被雌二醇抑制表达的凋亡基因中，有编码1型InsP3R的ITPR1。InsP3Rs是细胞内钙通道和关键的促凋亡介质。雌二醇通过雌激素受体β1抑制G-292细胞ITPR1基因转录。这些分析表明，雌激素在对抗骨质疏松中有益活性的潜在基础可能与预防成骨细胞凋亡有关，而这一过程中的一个关键事件是抑制凋亡基因表达和抑制caspase-3/7。
Dysregulated apoptosis is a critical failure associated with prominent degenerative diseases including osteoporosis. In bone, estrogen deficiency has been associated with accelerated osteoblast apoptosis and susceptibility to osteoporotic fractures. Hormone therapy continues to be an effective option for preventing osteoporosis and bone fractures. Induction of apoptosis in G-292 human osteoblastic cells by exposure to etoposide or the inflammatory cytokine TNFα promoted acute caspase-3/7 activity and this increased activity was inhibited by pretreatment with estradiol. Etoposide also increased the expression of a battery of apoptosis-promoting genes and this expression was also inhibited by estradiol. Among the apoptotic genes whose expression was inhibited by estradiol was ITPR1, which encodes the type 1 InsP3R. InsP3Rs are intracellular calcium channels and key proapoptotic mediators. Estradiol via estrogen receptor β1 suppresses ITPR1 gene transcription in G-292 cells. These analyses suggest that an underlying basis of the beneficial activity of estrogens in combating osteoporosis may involve the prevention of apoptosis in osteoblasts and that a key event in this process is the repression of apoptotic gene expression and inhibition of caspase-3/7.
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影响因子：
4.8
作者：
Kirkwood, KL;Homick, K;Bradford, PG
通讯作者：
Bradford, PG
影响因子：
4.1
作者：
Martin, R. B.
通讯作者：
Martin, R. B.
影响因子：
120.7
作者：
Speroff, L;Rowan, J;Wilborn, W
通讯作者：
Wilborn, W
DOI：
10.1073/pnas.0702489104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Li, Chi;Wang, Xiaoli;White, Carl
通讯作者：
White, Carl
影响因子：
2.8
作者：
Middleton, E. T.;Steel, S. A.
通讯作者：
Steel, S. A.