IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26302-y.html
   My bibliography  Save this article

Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors

Author

Listed:
  • Wei Xia

    (Southern Medical University)

  • Jing Xie

    (Southern Medical University)

  • Zhiqing Cai

    (Southern Medical University)

  • Xuhua Liu

    (The Third Affiliated Hospital of Southern Medical University)

  • Jing Wen

    (Nanfang Hospital, Southern Medical University)

  • Zhong-Kai Cui

    (Southern Medical University)

  • Run Zhao

    (Southern Medical University)

  • Xiaomei Zhou

    (Southern Medical University)

  • Jiahui Chen

    (The Third Affiliated Hospital of Southern Medical University)

  • Xinru Mao

    (Nanfang Hospital, Southern Medical University)

  • Zhengtao Gu

    (Southern Medical University)

  • Zhimin Zou

    (Southern Medical University)

  • Zhipeng Zou

    (Southern Medical University)

  • Yue Zhang

    (Southern Medical University)

  • Ming Zhao

    (Southern Medical University)

  • Maegele Mac

    (Private University of Witten-Herdecke, Cologne Merheim Medical Center)

  • Qiancheng Song

    (Southern Medical University)

  • Xiaochun Bai

    (Southern Medical University)

Abstract

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3′UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.

Suggested Citation

  • Wei Xia & Jing Xie & Zhiqing Cai & Xuhua Liu & Jing Wen & Zhong-Kai Cui & Run Zhao & Xiaomei Zhou & Jiahui Chen & Xinru Mao & Zhengtao Gu & Zhimin Zou & Zhipeng Zou & Yue Zhang & Ming Zhao & Maegele M, 2021. "Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26302-y
    DOI: 10.1038/s41467-021-26302-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26302-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26302-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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 Wan, 2016. "Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation," Nature Communications, Nature, vol. 7(1), pages 1-16, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuanyuan Yu & Luyao Wang & Shuaijian Ni & Dijie Li & Jin Liu & Hang Yin Chu & Ning Zhang & Meiheng Sun & Nanxi Li & Qing Ren & Zhenjian Zhuo & Chuanxin Zhong & Duoli Xie & Yongshu Li & Zong-Kang Zhang, 2022. "Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Chuanxin Zhong & Nanxi Li & Shengzheng Wang & Dijie Li & Zhihua Yang & Lin Du & Guangxin Huang & Haitian Li & Wing Sze Yeung & Shan He & Shuting Ma & Zhuqian Wang & Hewen Jiang & Huarui Zhang & Zhangh, 2024. "Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26302-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.