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

نویسندگان

  • 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
  • De-An Guo
  • Hailong Zhu
  • Weihong Tan
  • Aiping Lu
  • Ge Zhang
چکیده

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.

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عنوان ژورنال:
  • Nature communications

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016