期刊
RNA BIOLOGY
卷 12, 期 3, 页码 343-353出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2015.1017205
关键词
miRNA; osteoclast; osteoporosis; PTEN; PI 3-kinase
资金
- National Natural Science Foundation of China [31325012, 31170811, 31271225, 31340064, 81370971]
- National Basic Research 973 Program of China [2011CB711003]
- State Key Lab of Space Medicine Fundamentals and Application grant [SMFA13A02]
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-kappa B 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.
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