Chinese Journal of Tissue Engineering Research ›› 2018, Vol. 22 ›› Issue (32): 5139-5144.doi: 10.3969/j.issn.2095-4344.0931

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Interactions of Notch signaling pathway and miR-21 in peripheral nerve repair

Yang Kai-yun, Sun Pei-pei, Wu Wen-liang, Liu Hai-chun   

  1. Department of Orthopedics, Shandong University Qilu Hospital, Jinan 250012, Shandong Province, China
  • Received:2018-03-05 Online:2018-11-18 Published:2018-11-18
  • Contact: Liu Hai-chun, M.D., Associate chief physician, Department of Orthopedics, Shandong University Qilu Hospital, Jinan 250012, Shandong Province, China
  • About author:Yang Kai-yun, Master, Research assistant, Department of Orthopedics, Shandong University Qilu Hospital, Jinan 250012, Shandong Province, China
  • Supported by:

    the Key Research and Development Program of Shandong Province, No. 2017GSF218047

Abstract:

BACKGROUND: Nerve injury repair is one of the major surgical hot spots in clinical and basic research. Small-gap sleeve method has been confirmed to have therapeutic effects on peripheral nerve injuries, but the detailed mechanism is unclear. The Notch signaling pathway and the microRNA system have gradually become potential hotspots in this field, but their interactions have not yet been clearly reported.
OBJECTIVE: To observe the performance of bone marrow mesenchymal stem cells-packed small-gap sleeve in the treatment of peripheral nerve injuries and to explore the interactions of Notch signaling pathway and miR-21 during the repair process.
METHODS: Models of 8 mm-recurrent laryngeal nerve defects were made in Sprague-Dawley rats and randomly divided into three groups: sham operation group, small-gap sleeve group and combined group (small-gap sleeve carrying bone marrow mesenchymal stem cells). After transplantation, neuroelectrophysiological results were measured, and the expression of Notch signal and miR-21 was determined by western blot assay. Bone marrow mesenchymal stem cells cultured in a small-gap sleeve undertook neuronal induction. By changing the expression of Notch/miR21, we detected the expression of neural markers and analyzed the activity of bone marrow mesenchymal stem cells.
RESULTS AND CONCLUSION: Transplantation of bone marrow mesenchymal stem cells had therapeutic effects on peripheral nerve injuries as confirmed by neurostaining and electromyogram. During the neural differentiation of bone marrow mesenchymal stem cells, the expressions of Notch signal and miR-21 were significantly increased. Activation of Notch signal or miR-21 overexpression could strengthen the neural differentiation of bone marrow mesenchymal stem cells, while inhibition of Notch signal weakened the neural differentiation of bone marrow mesenchymal stem cells, and miR-21 lost its promotion effect. Overall, Notch signaling pathway and miR-21 are considered to promote the therapeutic effects of bone marrow mesenchymal stem cells combined with small-gap sleeve for peripheral nerve injuries, in which Notch signaling pathway has stronger promotion or inhibition roles.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松组织工程

Key words: Receptors, Notch, MicroRNAs, Peripheral Nerves, Tissue Engineering

CLC Number: