FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice.
FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice.
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DOI：
10.1016/j.cmet.2009.12.009
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发表时间：
2010-02-03
期刊：
影响因子：
29
通讯作者：
Manolagas SC
中科院分区：
文献类型：
--
作者：
Ambrogini E;Almeida M;Martin-Millan M;Paik JH;Depinho RA;Han L;Goellner J;Weinstein RS;Jilka RL;O'Brien CA;Manolagas SC
衰老增加氧化应激和成骨细胞凋亡，并减少骨量，而叉头盒O（FoxO）转录因子通过激活参与自由基清除和凋亡的基因来防御氧化应激。在三个月大的小鼠中，FoxO1、3和4的条件性缺失导致骨氧化应激和成骨细胞凋亡增加，成骨细胞数量减少，骨形成率降低，松质骨和皮质骨骨量减少。该基因缺失对成骨细胞凋亡的影响是细胞自主性的，是氧化应激的结果。相反，在成熟成骨细胞中过表达FoxO3转基因降低了氧化应激和成骨细胞凋亡，并增加了成骨细胞数量、骨形成率和椎骨骨量。我们的结论是FoxO依赖的氧化防御提供了一种机制来处理成骨细胞有氧代谢不断产生的氧自由基，从而是骨量稳态不可或缺的。
Aging increases oxidative stress and osteoblast apoptosis and decreases bone mass, whereas forkhead box O (FoxO) transcription factors defend against oxidative stress by activating genes involved in free radical scavenging and apoptosis. Conditional deletion of FoxO1, 3 and 4 in three month-old mice resulted in an increase in oxidative stress in bone and osteoblast apoptosis and a decrease in the number of osteoblasts, the rate of bone formation, and bone mass at cancellous and cortical sites. The effect of the deletion on osteoblast apoptosis was cell autonomous and resulted from oxidative stress. Conversely, overexpression of a FoxO3 transgene in mature osteoblasts decreased oxidative stress and osteoblast apoptosis, and increased osteoblast number, bone formation rate and vertebral bone mass. We conclude that FoxO-dependent oxidative defense provides a mechanism to handle the oxygen free radicals constantly generated by the aerobic metabolism of osteoblasts and is thereby indispensable for bone mass homeostasis.
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影响因子：
4.1
作者：
Jilka, Robert L.;O'Brien, Charles A.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
通讯作者：
Manolagas, Stavros C.
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
4.8
作者：
Armoni, Michal;Harel, Chava;Karnieli, Eddy
通讯作者：
Karnieli, Eddy
影响因子：
4.8
作者：
Almeida, Maria;Ambrogini, Elena;Jilka, Robert L.
通讯作者：
Jilka, Robert L.