title: Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity.
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.
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China; Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China; Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Orthopedics, 309 Hospital of Chinese People's Liberation Army , Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chinese Academy of Sciences for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
authors.affiliation: Institute of Orthopedics, General Hospital of Chinese People's Liberation Army , Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Orthopedics, General Hospital of Chinese People's Liberation Army , Beijing, China.
authors.forename: Aiyuan
authors.initials: A
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China; Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology , Harbin, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Orthopedics, General Hospital of Chinese People's Liberation Army , Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Orthopedics, General Hospital of Chinese People's Liberation Army , Beijing, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Chinese Academy of Sciences for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China; Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Bingxing
authors.initials: B
authors.lastname: Han
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.affiliation: Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University , Shijiazhuang, China.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center , Beijing, China.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
keywords: exosome; miRNA; osteoblast; osteoclast