[HTML][HTML] Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

D Li, J Liu, B Guo, C Liang, L Dang, C Lu, X He… - Nature …, 2016 - nature.com
D Li, J Liu, B Guo, C Liang, L Dang, C Lu, X He, HYS Cheung, L Xu, C Lu, B He, B Liu…
Nature communications, 2016nature.com
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs
(miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However,
whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly
unknown. Here, we show that increased osteoclastic miR-214-3p associates with both
elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with
fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice …
Abstract
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
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