@article{3f95040379cc4b2f91d55d45962e4fc5,
title = "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.",
author = "Defang LI and Jin LIU and Baosheng GUO and Chao LIANG and Lei Dang and Cheng Lu and Xiaojuan He and Cheung, \{Hilda Yeuk Siu\} and Liang Xu and Changwei Lu and Bing He and Biao Liu and Shaikh, \{Atik Badshah\} and Fangfei LI and Luyao Wang and Zhijun YANG and Au, \{Doris Wai Ting\} and Songlin Peng and Zongkang Zhang and Zhang, \{Bao Ting\} and Xiaohua Pan and Airong Qian and Peng Shang and Lianbo Xiao and Baohong Jiang and WONG, \{Chris K C\} and Jiake Xu and Zhaoxiang BIAN and Zicai Liang and Guo, \{De An\} and Hailong ZHU and Weihong Tan and Aiping LYU and Ge ZHANG",
note = "Funding Information: We thank the technical staff from Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University for providing critical comments and technical support. This study was supported by the Ministry of Science and Technology of China (2013ZX09301307 to A.L.), the Hong Kong General Research Fund (HKBU479111 to G.Z., HKBU478312 to G.Z., HKBU262913 to G.Z., HKBU12102914 to G.Z., HKBU261113 to A.L. HKBU212111 to H.Z., HKBU212613 to H.Z., CUHK14112915 to B.Z. and CUHK489213 to B.Z.), the Natural Science Foundation Council of China (81272045 to G.Z., 81272045 to B.G., 81401833 to B.G. and 81470072 to X.H.), the Research Grants Council and Natural Science Foundation Council of China (N\_HKBU435/12 to G.Z.), the Croucher Foundation (Gnt\#CAS14BU/CAS14201 to G.Z.), the Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/12-13/02 to A.L. and RC-IRMS/13-14/02 to G.Z.), the Hong Kong Baptist University Strategic Development Fund (SDF13-1209-P01 to A.L.), the Hong Kong Research Grants Council Early Career Scheme (489213 to G.Z.), the Inter-institutional Collaborative Research Scheme of Hong Kong Baptist University (RC-ICRS/ 14-15/01 to G.Z.), the Faculty Research Grant of Hong Kong Baptist University (FRG1/ 13-14/024 to G.Z., FRG2/13-14/006 to G.Z., FRG2/14-15/010 to G.Z. and FRG2/14-15/ 063 to H.Z.), the China Academy of Chinese Medical Sciences (Z0252 and Z0293 to A.L.). The statistical analysis was performed by a contract service from Bioinformedicine (http://www.bioinformedicine.com/index.php).",
year = "2016",
month = mar,
day = "7",
doi = "10.1038/ncomms10872",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
}