title: miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway.
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.
authors.affiliation: a From Key Laboratory of Molecular and Cellular Biology of Ministry of Education; College of Life Science; Hebei Normal University ; Shijiazhuang , China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhao
authors.forename: Weijia
authors.initials: W
authors.lastname: Sun
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Li
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Zhao
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.forename: Aiyuan
authors.initials: A
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jinping
authors.initials: J
authors.lastname: Song
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Xu
authors.forename: Zi
authors.initials: Z
authors.lastname: Xu
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhong
authors.forename: Bingxing
authors.initials: B
authors.lastname: Han
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D015519:Bone Density; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D009841:Oligonucleotides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
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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