Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts.
Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts.
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DOI：
10.18632/aging.203639
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发表时间：
2021-10-28
期刊：
影响因子：
--
通讯作者：
Guo L
中科院分区：
文献类型：
--
作者：
Wang Y;Mei R;Hao S;Luo P;Wang P;Almatari Y;Guo L;Guo L
骨质疏松症是一种常见的全身骨骼代谢紊乱，导致骨骼脆弱和骨折风险增加。沉默信息调节因子2同源物1 （SIRT1）在骨代谢、自噬、细胞凋亡和衰老等多种生物过程的调控中起着至关重要的作用。本研究旨在评估17β-雌二醇（17β-E2）诱导SIRT1上调是否分别通过AMPK-mTOR和FOXO3a途径促进成骨细胞自噬和抑制细胞凋亡。研究发现，17β-E2 （10-6 M）给药可诱导成骨细胞SIRT1上调。17β-E2诱导SIRT1上调后，LC3、Beclin-1、Bcl-2、p-AMPK、FOXO3a表达水平升高，caspase-3、p-mTOR表达水平降低，促进细胞自噬，抑制细胞凋亡。透射电镜下观察到17β-E2和SRT1720（一种选择性SIRT1激活剂）共处理组的自噬体增多。当预处理Ex527（一种sirt1特异性抑制剂）时，观察到相反的变化。综上所述，我们的研究结果表明，17β-E2诱导SIRT1上调可通过AMPK-mTOR途径促进自噬，并通过FOXO3a激活抑制成骨细胞凋亡，SIRT1可能成为骨质疏松症治疗中更重要的靶点。
Osteoporosis is a common systemic skeletal metabolism disorder resulting in bone fragility and increased fracture risk. Silent information regulator factor 2 homolog 1 (SIRT1) is crucial in the regulation of several biological processes, including bone metabolism, autophagy, apoptosis, and aging. This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17β-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively. The study found that 17β-E2 (10-6 M) administration induced the up-regulation of SIRT1 in osteoblasts. Up-regulation of SIRT1 induced by 17β-E2 increased the expression level of LC3, Beclin-1, Bcl-2, p-AMPK, FOXO3a but decreased caspase-3 and p-mTOR expression, and then promoted autophagy and inhibited apoptosis. More autophagosomes were observed under a transmission electron microscope (TEM) in 17β-E2 and SRT1720 (a selective SIRT1 activator) co-treated group. When Ex527 (a SIRT1-specific inhibitor) was pretreated, the reversed changes were observed. Taken together, our findings demonstrated that the up-regulation of SIRT1 induced by 17β-E2 could promote autophagy via the AMPK-mTOR pathway and inhibit apoptosis via the FOXO3a activation in osteoblasts, and SIRT1 might become a more significant target in osteoporosis treatment.
DOI：
10.18632/aging.100272
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Calvanese V;Fraga MF
通讯作者：
Fraga MF