<scp>EPC</scp>‐derived exosomes promote osteoclastogenesis through Lnc<scp>RNA</scp>‐<scp>MALAT</scp>1
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- Yigong Cui
- Department of Orthopaedics Southwest Hospital The Third Military Medical University Chongqing P.R. China
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- Shenglong Fu
- Department of Orthopaedics Jinan Fifth People's Hospital Shandong P.R. China
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- Dong Sun
- Department of Orthopaedics Southwest Hospital The Third Military Medical University Chongqing P.R. China
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- Junchao Xing
- Department of Orthopaedics Southwest Hospital The Third Military Medical University Chongqing P.R. China
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- Tianyong Hou
- Department of Orthopaedics Southwest Hospital The Third Military Medical University Chongqing P.R. China
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- Xuehui Wu
- Department of Orthopaedics Southwest Hospital The Third Military Medical University Chongqing P.R. China
Abstract
<jats:title>Abstract</jats:title><jats:p>Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (<jats:styled-content style="fixed-case">EPC</jats:styled-content>s). However, the role of <jats:styled-content style="fixed-case">EPC</jats:styled-content>s in osteoclastogenesis is unclear. In this study, we assess the effects of <jats:styled-content style="fixed-case">EPC</jats:styled-content>‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages (<jats:styled-content style="fixed-case">BMM</jats:styled-content>s) in vitro using immunofluorescence, western blotting, <jats:styled-content style="fixed-case">RT</jats:styled-content>‐<jats:styled-content style="fixed-case">PCR</jats:styled-content> and Transwell assays. We also evaluated the effects of <jats:styled-content style="fixed-case">EPC</jats:styled-content>‐derived exosomes on the homing and osteoclastic differentiation of transplanted <jats:styled-content style="fixed-case">BMM</jats:styled-content>s in a mouse bone fracture model in vivo. We found that <jats:styled-content style="fixed-case">EPC</jats:styled-content>s cultured with <jats:styled-content style="fixed-case">BMM</jats:styled-content>s secreted exosomes into the medium and, compared with <jats:styled-content style="fixed-case">EPC</jats:styled-content>s, exosomes had a higher expression level of Lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐<jats:styled-content style="fixed-case">MALAT</jats:styled-content>1. We confirmed that Lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐<jats:styled-content style="fixed-case">MALAT</jats:styled-content>1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of <jats:styled-content style="fixed-case">BMM</jats:styled-content>s induced by <jats:styled-content style="fixed-case">EPC</jats:styled-content>‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin <jats:styled-content style="fixed-case">ITGB</jats:styled-content>1 is the target of miR‐124. Mice treated with <jats:styled-content style="fixed-case">EPC</jats:styled-content>‐derived exosome‐<jats:styled-content style="fixed-case">BMM</jats:styled-content> co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with <jats:styled-content style="fixed-case">BMM</jats:styled-content>s alone. Overall, our results suggest that <jats:styled-content style="fixed-case">EPC</jats:styled-content>‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through Lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐<jats:styled-content style="fixed-case">MALAT</jats:styled-content>1.</jats:p>
Journal
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- Journal of Cellular and Molecular Medicine
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Journal of Cellular and Molecular Medicine 23 (6), 3843-3854, 2019-04-25
Wiley
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Details 詳細情報について
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- CRID
- 1360857595286053888
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- ISSN
- 15824934
- 15821838
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- Data Source
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- Crossref