miR-146a-5p targets Sirt1 to regulate bone mass.
miR-146a-5p targets Sirt1 to regulate bone mass.
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miR-146a-5p 靶向 Sirt1 调节骨量
DOI：
10.1016/j.bonr.2021.101013
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发表时间：
2021-06
期刊：
影响因子：
2.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Zheng M;Tan J;Liu X;Jin F;Lai R;Wang X
microRNA（miRNAs）已被证明是关键的转录后调节因子，影响包括成骨分化和骨形成在内的多种生物学过程。最近，有报道说miR-146 a-5 p影响成骨细胞和破骨细胞的活性。然而，这些方法中miR-146 a-5 p的靶基因仍然未知。在这里，我们确定miR-146 a-5 p作为成骨细胞和骨形成的关键抑制因子。我们发现miR-146 a-5 p敲除小鼠体内骨形成和骨量增加。同时，我们还发现miR-146 a-5 p在体外抑制骨髓间充质干细胞（BMSCs）向成骨细胞的分化。重要的是，我们进一步证明了miR-146 a-5 p直接靶向Sirt 1以抑制成骨细胞活性。此外，我们发现，不仅在雌性小鼠中，而且在雌性患者中，随着年龄的增长，股骨中miR-146 a-5 p的表达逐渐增加，miR-146 a-5 p缺失保护雌性小鼠免受年龄诱导的骨丢失。这些数据表明，miR-146 a-5 p在抑制骨形成中具有关键作用，抑制miR-146 a-5 p可能是改善骨质疏松症的策略。miR-146 a-5 p通过靶向Sirt 1抑制成骨细胞活性。MiR-146 a-5 p缺失改善小鼠中年龄诱导的骨丢失MiR-146 a-5 p表达在来自老年女性的骨标本中增加。miR-146 a-5 p是骨质疏松症治疗的潜在靶点。
MicroRNAs (miRNAs) have been proven to serve as key post-transcriptional regulators, affecting diverse biological processes including osteogenic differentiation and bone formation. Recently, it has been reported that miR-146a-5p affects the activity of both osteoblasts and osteoclasts. However, the target genes of miR-146a-5p in these procedures remain unknown. Here we identify miR-146a-5p as a critical suppressor of osteoblastogenesis and bone formation. We found that miR-146a-5p knockout mice exhibit elevated bone formation and enhanced bone mass in vivo. Consistently, we also found that miR-146a-5p inhibited the osteoblast differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Importantly, we further demonstrated that miR-146a-5p directly targeted Sirt1 to inhibit osteoblast activity. Additionally, we showed that the expression of miR-146a-5p gradually increased in femurs with age not only in female mice but also in female patients, and miR-146a-5p deletion protected female mice from age-induced bone loss. These data suggested that miR-146a-5p has a crucial role in suppressing the bone formation and that inhibition of miR-146a-5p may be a strategy for ameliorating osteoporosis. MiR-146a-5p inhibits osteoblast activity by targeting Sirt1. MiR-146a-5p deletion ameliorates age-induced bone loss in mice. MiR-146a-5p expression was increased in bone specimens from older females. MiR-146a-5p was a potential target for osteoporosis treatment.
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影响因子：
4.8
作者：
Cohen-Kfir, Einav;Artsi, Hanna;Dresner-Pollak, Rivka
通讯作者：
Dresner-Pollak, Rivka
影响因子：
--
作者：
Gabay, Odile;Sanchez, Christelle;Dvir-Ginzberg, Mona;Gagarina, Viktoria;Zaal, Kristien J.;Song, Yingjie;He, Xiao Hong;McBurney, Michael W.
通讯作者：
McBurney, Michael W.
影响因子：
4.8
作者：
Artsi, Hanna;Cohen-Kfir, Einav;Dresner-Pollak, Rivka
通讯作者：
Dresner-Pollak, Rivka
影响因子：
29
作者：
Berger, Julian Meyer;Singh, Parminder;Karsenty, Gerard
通讯作者：
Karsenty, Gerard
老年人的骨质疏松和脆弱的概述。
影响因子：
2.3
作者：
Li G;Thabane L;Papaioannou A;Ioannidis G;Levine MA;Adachi JD
通讯作者：
Adachi JD