Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10872
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Funding
- Ministry of Science and Technology of China [2013ZX09301307]
- Hong Kong General Research Fund [HKBU479111, HKBU478312, HKBU262913, HKBU12102914, HKBU261113, HKBU212111, HKBU212613, CUHK14112915, CUHK489213]
- Natural Science Foundation Council of China [81272045, 81401833, 81470072, N_HKBU435/12]
- Research Grants Council
- Croucher Foundation [CAS14BU/CAS14201]
- Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University [RC-IRMS/12-13/02, RC-IRMS/13-14/02]
- Hong Kong Baptist University Strategic Development Fund [SDF13-1209-P01]
- Hong Kong Research Grants Council Early Career Scheme [489213]
- Inter-institutional Collaborative Research Scheme of Hong Kong Baptist University [RC-ICRS/14-15/01]
- Faculty Research Grant of Hong Kong Baptist University [FRG1/13-14/024, FRG2/13-14/006, FRG2/14-15/010, FRG2/14-15/063]
- China Academy of Chinese Medical Sciences [Z0252, Z0293]
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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 osteoclastderived 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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