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 ZhangXiaohua Pan, Airong Qian, Peng Shang, Lianbo Xiao, Baohong Jiang, Chris K C WONG, Jiake Xu, Zhaoxiang BIAN, Zicai Liang, De An Guo, Hailong ZHU, Weihong Tan, Aiping LYU, Ge ZHANG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

206 Citations (Scopus)

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.

Original languageEnglish
Article number10872
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 7 Mar 2016

Scopus Subject Areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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