title: Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.
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.
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.
authors.forename: Defang
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.|Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dang
authors.affiliation: Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Hilda Yeuk-Siu
authors.initials: HY
authors.lastname: Cheung
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Atik Badshah
authors.initials: AB
authors.lastname: Shaikh
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Fangfei
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR 999077, China.
authors.forename: Doris Wai-Ting
authors.initials: DW
authors.lastname: Au
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Department of Spine Surgery, Shenzhen People's Hospital, Ji Nan University Second College of Medicine, Shenzhen 518020, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Peng
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR 999077, China.
authors.forename: Zongkang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR 999077, China.
authors.forename: Bao-Ting
authors.initials: BT
authors.lastname: Zhang
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Department of Orthopaedics and Traumatology, Bao'an Hospital Affiliated to Southern Medical University and Shenzhen 8th People Hospital, Shenzhen 518100, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.|Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.
authors.forename: Airong
authors.initials: A
authors.lastname: Qian
authors.affiliation: Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.|Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Baohong
authors.initials: B
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authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China.
authors.forename: Chris Kong-Chu
authors.initials: CK
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authors.affiliation: Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6907, Australia.
authors.forename: Jiake
authors.initials: J
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authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.
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authors.affiliation: Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
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authors.initials: Z
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authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: De-An
authors.initials: DA
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authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
authors.forename: Hailong
authors.initials: H
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authors.affiliation: Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.|Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.|Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.|Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.|Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.|Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D050723:Fractures, Bone / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*
chemical_list: C547397:MIRN214 microRNA, human; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse