Wang Dong, Diao Shuo, Zhou Xiaobin, Zhou Junlin, Liu Yang
Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Third Department of Traumatology, The Third Hospital of Shijiazhuang, Shijiazhuang 050000, China.
Injury. 2024 Feb;55(2):111210. doi: 10.1016/j.injury.2023.111210. Epub 2023 Nov 14.
Post-injury adaptation (PIA) is a simple and convenient method to promote bone healing, but its mechanism is unclear. This study was to discuss the role of fracture site tissue exosomes lncRNAs-mRNAs networks on PIA promoting bone mesenchymal stem cells (BMSCs) proliferation and migration. Firstly, the effects of PIA accelerating BMSCs proliferation and migration were confirmed by rat fracture model and bone fracture environment in vitro. Besides, the fracture site tissue exosomes were isolated and authenticated. Then the tissue exosomes were the key factor in PIA promoting BMSCs proliferation and migration authenticated by in vitro and in vivo experiments. The high throughput sequencing and RT-PCR were used to analyze the tissue exosomes lncRNAs-mRNAs networks. It was found that PIA treatment upregulated 118 lncRNAs, 295 mRNAs, and downregulated 111 lncRNAs, 2706 mRNAs in tissue exosomes. A total 12,211 genes were the target genes. Akt1, Actb and Uba52 were the hub mRNAs in tissue exosomes. In additions, tissue-derived exosomes of PIA treated rats upregulated 49 genes, 3 lncRNAs and downregulated 28 genes, 1 lncRNA in BMSCs. Kif11 was the hub gene. Overall, PIA promoted BMSCs proliferation and migration in the early stage of fracture healing, which was closely related to the fracture site tissue exosomes. Akt1, Actb and Uba52 were the hub mRNAs in the exosomes. Besides, Kif11 might be the key gene in BMSC regulated by tissue-derived exosomes of PIA treated rats.
损伤后适应性（PIA）是一种促进骨愈合的简单便捷方法，但其机制尚不清楚。本研究旨在探讨骨折部位组织外泌体lncRNAs-mRNAs网络在PIA促进骨间充质干细胞（BMSCs）增殖和迁移中的作用。首先，通过大鼠骨折模型和体外骨折环境证实了PIA促进BMSCs增殖和迁移的作用。此外，分离并鉴定了骨折部位组织外泌体。然后，通过体内外实验证实组织外泌体是PIA促进BMSCs增殖和迁移的关键因素。采用高通量测序和RT-PCR分析组织外泌体lncRNAs-mRNAs网络。结果发现，PIA处理使组织外泌体中118个lncRNAs、295个mRNAs上调，111个lncRNAs、2706个mRNAs下调。共有12211个基因是靶基因。Akt1、Actb和Uba52是组织外泌体中的核心mRNAs。此外，PIA处理大鼠的组织来源外泌体使BMSCs中49个基因、3个lncRNAs上调，28个基因、1个lncRNAs下调。Kif11是核心基因。总体而言，PIA在骨折愈合早期促进BMSCs增殖和迁移，这与骨折部位组织外泌体密切相关。Akt1、Actb和Uba52是外泌体中的核心mRNAs。此外，Kif11可能是PIA处理大鼠组织来源外泌体调控BMSC的关键基因。
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