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RNA Biol. 2015;12(3):343-53. doi: 10.1080/15476286.2015.1017205.

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

Author information

1
a From Key Laboratory of Molecular and Cellular Biology of Ministry of Education; College of Life Science; Hebei Normal University ; Shijiazhuang , China.

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.

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

PMID:
25826666
PMCID:
PMC4615895
DOI:
10.1080/15476286.2015.1017205
[Indexed for MEDLINE]
Free PMC Article

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