| Literature DB >> 25826666 |
Chenyang Zhao1, Weijia Sun, Pengfei Zhang, Shukuan Ling, Yuheng Li, Dingsheng Zhao, Jiang Peng, Aiyuan Wang, Qi Li, Jinping Song, Cheng Wang, Xiaolong Xu, Zi Xu, Guohui Zhong, Bingxing Han, Yan-Zhong Chang, Yingxian Li.
Abstract
microRNA is necessary for osteoclast differentiation, function and survival. It has been reported that miR-199/214 cluster plays important roles in vertebrate skeletal development and miR-214 inhibits osteoblast function by targeting ATF4. Here, we show that miR-214 is up-regulated during osteoclastogenesis from bone marrow monocytes (BMMs) with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induction, which indicates that miR-214 plays a critical role in osteoclast differentiation. Overexpression of miR-214 in BMMs promotes osteoclastogenesis, whereas inhibition of miR-214 attenuates it. We further find that miR-214 functions through PI3K/Akt pathway by targeting phosphatase and tensin homolog (Pten). In vivo, osteoclast specific miR-214 transgenic mice (OC-TG214) exhibit down-regulated Pten levels, increased osteoclast activity, and reduced bone mineral density. These results reveal a crucial role of miR-214 in the differentiation of osteoclasts, which will provide a potential therapeutic target for osteoporosis.Entities:
Keywords: BMD, bone mineral density; BMMs, bone marrow monocytes; BV/TV, ratio of bone volume to tissue volume; Dnm3os, Dnm3 opposite strand; M-CSF, macrophage colony stimulating factor; NFATc1, nuclear factor of activated T-cells cytoplasmic; OC-TG214, osteoclast specific miR-214 transgenic mice; PI 3-kinase; PTEN; Pten, phosphatase and tensin homolog; RANKL, receptor activator of nuclear factor-κB ligand; TRAP, tartrate-resistant acid phosphatase; Tb.Sp, trabecular spacing; WT, wild-type; miRNA; micro CT, Micro computed tomography; osteoclast; osteoporosis; qRT-PCR, quantitative real-time PCR
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Year: 2015 PMID： 25826666 PMCID： PMC4615895 DOI： 10.1080/15476286.2015.1017205
Source DB: PubMed Journal: RNA Biol ISSN： 1547-6286 Impact factor: 4.652