Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual.
Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual.
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DOI：
10.1084/jem.20102608
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发表时间：
2011-04-11
期刊：
影响因子：
--
通讯作者：
Karsenty G
中科院分区：
文献类型：
--
作者：
Kajimura D;Hinoi E;Ferron M;Kode A;Riley KJ;Zhou B;Guo XE;Karsenty G
交感神经系统通过CREB和ATF 4在成骨细胞中分别促进增殖和RANKL产生的信号传导来调节骨量增加。交感神经系统的活动受大脑中瘦素信号的调节，是骨量增加的主要调节器。为了确定交感神经紧张信号抑制骨量增加的细胞类型，我们对β2肾上腺素能受体（Adrβ2）的功能和小鼠途径中涉及的各种基因进行了系统的细胞特异性分析。随后进行瘦素脑室内（ICV）输注和骨参数的骨组织形态计量学分析。我们发现，成骨细胞中的交感神经紧张信号抑制CREB（cAMP反应元件结合蛋白）磷酸化，从而降低成骨细胞增殖，促进ATF 4磷酸化，从而增加RANKL（NF-κB配体受体激活剂）表达，然后刺激破骨细胞分化。在各种小鼠模型中的瘦素ICV输注建立了瘦素依赖性抑制骨量增加依赖于成骨细胞中发生的两种转录事件。因此，本研究正式确定成骨细胞作为主要的细胞类型，其中的分子事件触发的交感神经调节骨量增加发生。因此，这表明抑制交感神经信号传导可能有益于治疗低骨量状况。
The sympathetic nervous system regulates bone mass accrual by signaling via CREB and ATF4 in osteoblasts to promote proliferation and RANKL production, respectively. The sympathetic nervous system, whose activity is regulated by leptin signaling in the brain, is a major regulator of bone mass accrual. To determine the identity of the cell type in which the sympathetic tone signals to inhibit bone mass accrual, we performed a systematic, cell-specific analysis of the function of the β2 adrenergic receptor (Adrβ2) and various genes implicated in the pathway in the mouse. This was followed by leptin intracerebroventricular (ICV) infusion and bone histomorphometric analyses of bone parameters. We show that the sympathetic tone signals in the osteoblasts to inhibit CREB (cAMP-responsive element-binding protein) phosphorylation and thus decrease osteoblast proliferation and to promote ATF4 phosphorylation and thus increase RANKL (receptor activator of NF-κB ligand) expression, which then stimulates osteoclast differentiation. Leptin ICV infusion in various mouse models established that leptin-dependent inhibition of bone mass accrual relies on both transcriptional events taking place in osteoblasts. Thus, this study formally identifies the osteoblast as the major cell type in which the molecular events triggered by the sympathetic regulation of bone mass accrual take place. As such, it suggests that inhibiting sympathetic signaling could be beneficial in the treatment of low bone mass conditions.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
2.5
作者：
CHAPPARD, D;PALLE, S;RIFFAT, G
通讯作者：
RIFFAT, G
影响因子：
64.5
作者：
Yadav VK;Oury F;Suda N;Liu ZW;Gao XB;Confavreux C;Klemenhagen KC;Tanaka KF;Gingrich JA;Guo XE;Tecott LH;Mann JJ;Hen R;Horvath TL;Karsenty G
通讯作者：
Karsenty G
DOI：
10.1073/pnas.0308744101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Elefteriou, F;Takeda, S;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
64.5
作者：
Yang, XG;Matsuda, K;Karsenty, G
通讯作者：
Karsenty, G