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Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1

Author

Listed:
  • Chen Xu

    (Naval Medical University)

  • Zicheng Zhang

    (Naval Medical University
    the Fouth Medical Center of PLA General Hospital
    Naval Medical University)

  • Ning Liu

    (Naval Medical University
    923th Hospital of the Joint Logistics Support Force of PLA)

  • Li Li

    (Naval Medical University)

  • Huajian Zhong

    (Naval Medical University)

  • Ruizhe Wang

    (Naval Medical University)

  • Qianghui Shi

    (Naval Medical University)

  • Zifan Zhang

    (Naval Medical University)

  • Leixin Wei

    (Naval Medical University)

  • Bo Hu

    (Naval Medical University)

  • Hao Zhang

    (967th Hospital of the Joint Logistics Support Force of PLA)

  • Xiaolong Shen

    (Naval Medical University)

  • Yue Wang

    (the Fouth Medical Center of PLA General Hospital)

  • Yang Liu

    (Naval Medical University)

  • Wen Yuan

    (Naval Medical University)

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is an emerging spinal disease caused by heterotopic ossification of the posterior longitudinal ligament. The pathological mechanism is poorly understood, which hinders the development of nonsurgical treatments. Here, we set out to explore the function and mechanism of small extracellular vesicles (sEVs) in OPLL. Global miRNA sequencings are performed on sEVs derived from ligament cells of normal and OPLL patients, and we have showed that miR-320e is abundantly expressed in OPLL-derived sEVs compare to other sEVs. Treatment with either sEVs or miR-320e significantly promote the osteoblastic differentiation of normal longitudinal ligament cells and mesenchymal stem cells and inhibit the osteoclastic differentiation of monocytes. Through a mechanistic study, we find that TAK1 is a downstream target of miR-320e, and we further validate these findings in vivo using OPLL model mice. Together, our data demonstrate that OPLL ligament cells secrete ossification-promoting sEVs that contribute to the development of ossification through the miR-320e/TAK1 axis.

Suggested Citation

  • Chen Xu & Zicheng Zhang & Ning Liu & Li Li & Huajian Zhong & Ruizhe Wang & Qianghui Shi & Zifan Zhang & Leixin Wei & Bo Hu & Hao Zhang & Xiaolong Shen & Yue Wang & Yang Liu & Wen Yuan, 2022. "Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29029-6
    DOI: 10.1038/s41467-022-29029-6
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    References listed on IDEAS

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    1. Haiyang Zhang & Ting Deng & Rui Liu & Ming Bai & Likun Zhou & Xia Wang & Shuang Li & Xinyi Wang & Haiou Yang & Jialu Li & Tao Ning & Dingzhi Huang & Hongli Li & Le Zhang & Guoguang Ying & Yi Ba, 2017. "Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
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