Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity

Weijia Sun, Chenyang Zhao, Yuheng Li, Liang Wang, Guangjun Nie, Jiang Peng, Aiyuan Wang, Pengfei Zhang, Weiming Tian, Qi Li, Jinping Song, Cheng Wang, Xiaolong Xu, Yanhua Tian, Dingsheng Zhao, Zi Xu, Guohui Zhong, Bingxing Han, Shukuan Ling, Yan Zhong ChangYingxian Li

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

MicroRNAs have an important role in bone homeostasis. However, the detailed mechanism of microRNA-mediated intercellular communication between bone cells remains elusive. Here, we report that osteoclasts secrete microRNA-enriched exosomes, by which miR-214 is transferred into osteoblasts to inhibit their function. In a coculture system, inhibition of exosome formation and secretion prevented miR-214 transportation. Exosomes specifically recognized osteoblasts through the interaction between ephrinA2 and EphA2. In osteoclast-specific miR-214 transgenic mice, exosomes were secreted into the serum, and miR-214 and ephrinA2 levels were elevated. Therefore, these exosomes have an inhibitory role in osteoblast activity. miR-214 and ephrinA2 levels in serum exosomes from osteoporotic patients and mice were upregulated substantially. These exosomes may significantly inhibit osteoblast activity. Inhibition of exosome secretion via Rab27a small interfering RNA prevented ovariectomized-induced osteoblast dysfunction in vivo. Taken together, these findings suggest that exosome-mediated transfer of microRNA plays an important role in the regulation of osteoblast activity. Circulating miR-214 in exosomes not only represents a biomarker for bone loss but could selectively regulate osteoblast function.

Original languageEnglish (US)
Article number16015
JournalCell Discovery
Volume2
DOIs
StatePublished - May 31 2016

Keywords

  • exosome
  • miRNA
  • osteoblast
  • osteoclast

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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