miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway

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 osteoclast...

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Veröffentlicht in:RNA biology 2015-03, Vol.12 (3), p.343-353
Hauptverfasser: Zhao, Chenyang, Sun, Weijia, Zhang, Pengfei, Ling, Shukuan, Li, Yuheng, Zhao, Dingsheng, Peng, Jiang, Wang, Aiyuan, Li, Qi, Song, Jinping, Wang, Cheng, Xu, Xiaolong, Xu, Zi, Zhong, Guohui, Han, Bingxing, Chang, Yan-Zhong, Li, Yingxian
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Sprache:eng
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Zusammenfassung: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.
ISSN:1547-6286
1555-8584
1555-8584
DOI:10.1080/15476286.2015.1017205