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Nat Commun. 2016 Mar 7;7:10872. doi: 10.1038/ncomms10872.

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

Li D1,2,3,4,5, Liu J1,2,3,4, Guo B1,2,3,4,5,6, Liang C1,2,3,4,7,8, Dang L1,2,3,4, Lu C2,9, He X1,9, Cheung HY1,6, Xu L1, Lu C1, He B1,2,3,4, Liu B1,2,3,4,6, Shaikh AB1,2,3,4, Li F1,2,3,4, Wang L1,2,3,4, Yang Z1,2,3,4,6, Au DW10, Peng S1,11, Zhang Z12, Zhang BT12, Pan X1,13, Qian A8,14, Shang P8,14, Xiao L1,15, Jiang B16, Wong CK17, Xu J18, Bian Z1,2,3, Liang Z4, Guo DA16, Zhu H1,2,3,4, Tan W7, Lu A1,2,3,4,5,6,7,8,9,15, Zhang G1,2,3,4,5,6,7,8,15.

Author information

1
Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
2
Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
3
Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.
4
Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
5
Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.
6
Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
7
Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.
8
Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.
9
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
10
Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR 999077, China.
11
Department of Spine Surgery, Shenzhen People's Hospital, Ji Nan University Second College of Medicine, Shenzhen 518020, China.
12
School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR 999077, China.
13
Department of Orthopaedics and Traumatology, Bao'an Hospital Affiliated to Southern Medical University and Shenzhen 8th People Hospital, Shenzhen 518100, China.
14
Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.
15
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
16
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
17
Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China.
18
Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6907, Australia.

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.

PMID:
26947250
PMCID:
PMC4786676
DOI:
10.1038/ncomms10872
[Indexed for MEDLINE]
Free PMC Article

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