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

Defang Li, Jin Liu, Baosheng Guo, Chao Liang, Lei Dang, Cheng Lu, Xiaojuan He, Hilda Yeuk-Siu Cheung, Liang Xu, Changwei Lu, Bing He, Biao Liu, Atik Badshah Shaikh, Fangfei Li, Luyao Wang, Zhijun Yang, Doris Wai-Ting Au, Songlin Peng, Zongkang Zhang, Bao-Ting Zhang, Xiaohua Pan, Airong Qian, Peng Shang, Lianbo Xiao, Baohong Jiang, Chris Kong-Chu Wong, Jiake Xu, Zhaoxiang Bian, Zicai Liang, Guo De-an, Hailong Zhu, Weihong Tan, Aiping Lu () and Ge Zhang ()
Additional contact information
Defang Li: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Jin Liu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Baosheng Guo: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Chao Liang: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Lei Dang: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Cheng Lu: Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
Xiaojuan He: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Hilda Yeuk-Siu Cheung: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Liang Xu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Changwei Lu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Bing He: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Biao Liu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Atik Badshah Shaikh: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Fangfei Li: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Luyao Wang: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Zhijun Yang: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Doris Wai-Ting Au: City University of Hong Kong
Songlin Peng: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Zongkang Zhang: School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong
Bao-Ting Zhang: School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong
Xiaohua Pan: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Airong Qian: Hong Kong Baptist University–Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space
Peng Shang: Hong Kong Baptist University–Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space
Lianbo Xiao: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Baohong Jiang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Chris Kong-Chu Wong: Hong Kong Baptist University
Jiake Xu: Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6907, Australia
Zhaoxiang Bian: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Zicai Liang: Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology
Guo De-an: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Hailong Zhu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Weihong Tan: Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University
Aiping Lu: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
Ge Zhang: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10872

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