SIRT3
粒体自噬
衰老
老年性骨质疏松症
自噬
细胞生物学
线粒体
锡尔图因
基因沉默
癌症研究
生物
间充质干细胞
细胞凋亡
骨质疏松症
内分泌学
NAD+激酶
生物化学
酶
基因
作者
Yuanyuan Guo,Jun Xiong,Yongzhi Cui,Yu Song,Siyuan Wang,Yongtao Geng,Rui Li,Weihang Gao,Dehao Fu
出处
期刊:Redox biology
[Elsevier]
日期:2021-05-01
卷期号:41: 101915-101915
被引量:120
标识
DOI:10.1016/j.redox.2021.101915
摘要
Senile osteoporosis (SOP) is widely regarded as one of the typical aging-related diseases due to a decrease in bone mass and the destruction in microarchitecture. The inhibition of mitophagy can promote bone marrow mesenchymal stem cells (BMSCs) senescence, and increasing studies have shown that interventions targeting BMSCs senescence can ameliorate osteoporosis, exhibiting their potential for use as therapeutic strategies. Sirtuin-3 (Sirt3) is an essential mitochondria metabolic regulatory enzyme that plays an important role in mitochondrial homeostasis, but its role in bone homeostasis remains largely unknown. This study seeks to investigate whether advanced glycation end products (AGEs) accumulation aggravated BMSCs senescence and SOP, and explored the mechanisms underlying these effects. We observed that AGEs significantly aggravated BMSCs senescence, as well as promoted mitochondrial dysfunction and inhibited mitophagy in a concentration-dependent manner. In addition, this effect could be further strengthened by Sirt3 silencing. Importantly, we identified that the reduction of Sirt3 expression and the mitophagy were vital mechanisms in AGEs-induced BMSCs senescence. Furthermore, overexpression of Sirt3 by intravenously injection with recombinant adeno-associated virus 9 carrying Sirt3 plasmids (rAAV-Sirt3) significantly alleviated BMSCs senescence and the formation of SOP in SAMP6. In conclusion, our data demonstrated that Sirt3 protects against AGEs-induced BMSCs senescence and SOP. Targeting Sirt3 to improve mitophagy may represent a potential therapeutic strategy for attenuating AGEs-associated SOP.
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