Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Li D,Liu J,Guo B,Liang C,Dang L,Lu C,He X,Cheung HY,Xu L,Lu C,He B,Liu B,Shaikh AB,Li F,Wang L,Yang Z,Au DW,Peng S,Zhang Z,Zhang BT,Pan X,Qian A,Shang P,Xiao L,Jiang B,Wong CK,Xu J,Bian Z,Liang Z,

doi

10.1038/ncomms10872

subject

Has Abstract

pub_date

2016-03-07 00:00:00

pages

10872

issn

2041-1723

pii

ncomms10872

journal_volume

7

pub_type

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