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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
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    References listed on IDEAS

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    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.
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