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

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 () and Wen Yuan ()
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Chen Xu: Naval Medical University
Zicheng Zhang: Naval Medical University
Ning Liu: Naval Medical University
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

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29029-6

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