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

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  • Defang Li

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Jin Liu

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Baosheng Guo

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Chao Liang

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Lei Dang

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Cheng Lu

    (Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences)

  • Xiaojuan He

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences)

  • Hilda Yeuk-Siu Cheung

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, 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
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Biao Liu

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Atik Badshah Shaikh

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Fangfei Li

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Luyao Wang

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Zhijun Yang

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • 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
    Shenzhen People’s Hospital, Ji Nan University Second College of Medicine)

  • 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
    Bao’an Hospital Affiliated to Southern Medical University and Shenzhen 8th People Hospital)

  • Airong Qian

    (Hong Kong Baptist University–Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space
    Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University)

  • Peng Shang

    (Hong Kong Baptist University–Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space
    Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University)

  • Lianbo Xiao

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences)

  • 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
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education)

  • Zicai Liang

    (Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • De-an Guo

    (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
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • 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
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

  • Ge Zhang

    (Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University
    Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University
    Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education
    Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology)

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.

Suggested Citation

  • 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 Wan, 2016. "Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation," Nature Communications, Nature, vol. 7(1), pages 1-16, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10872
    DOI: 10.1038/ncomms10872
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    Cited by:

    1. Wei Xia & Jing Xie & Zhiqing Cai & Xuhua Liu & Jing Wen & Zhong-Kai Cui & Run Zhao & Xiaomei Zhou & Jiahui Chen & Xinru Mao & Zhengtao Gu & Zhimin Zou & Zhipeng Zou & Yue Zhang & Ming Zhao & Maegele M, 2021. "Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Yuanyuan Yu & Luyao Wang & Shuaijian Ni & Dijie Li & Jin Liu & Hang Yin Chu & Ning Zhang & Meiheng Sun & Nanxi Li & Qing Ren & Zhenjian Zhuo & Chuanxin Zhong & Duoli Xie & Yongshu Li & Zong-Kang Zhang, 2022. "Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Chuanxin Zhong & Nanxi Li & Shengzheng Wang & Dijie Li & Zhihua Yang & Lin Du & Guangxin Huang & Haitian Li & Wing Sze Yeung & Shan He & Shuting Ma & Zhuqian Wang & Hewen Jiang & Huarui Zhang & Zhangh, 2024. "Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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