miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway.
RNA Biol
; 12(3): 343-53, 2015.
Article
en En
| MEDLINE
| ID: mdl-25826666
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.
Palabras clave
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
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteoclastos
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Osteoporosis
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Fosfatidilinositol 3-Quinasas
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MicroARNs
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Fosfohidrolasa PTEN
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Proteínas Proto-Oncogénicas c-akt
Límite:
Animals
Idioma:
En
Revista:
RNA Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
China