Cyclic mechanical stress modulates neurotrophic and myelinating gene expression of Schwann cells

周期性机械应力调节雪旺细胞的神经营养和髓鞘形成基因表达。

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Abstract

OBJECTIVES: This study aimed to investigate the response of Schwann cells to cyclic compressive and tensile stresses of different durations of stimulation. MATERIALS AND METHODS: RSC96 cells were subjected to cyclic tensile stress or compressive stress; for either, cells in five groups were treated for 0, 1, 2, 24 and 48 h respectively. Enzyme-linked immunosorbent assay was conducted to detect secretion of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4 in the culture medium. Real-time PCR was conducted to quantify mRNA expression of neurotrophins including NGF, BDNF, neurotrophin-3 and neurotrophin-4, and myelin-related genes including Sox10, Krox20, neuregulin 1, NCAM, N-cadherin, P0, MAG and MBP. Immunofluorescent staining was performed to visualize Krox20 and F-actin in the tensile groups. RESULTS: Within 24 h, cells treated with cyclic tensile stress expressed and secreted significantly more BDNF, while cyclic compression down-regulated BDNF expression. Cells treated with both tensile and compressive stress down-regulated expression of NRG1, NCAM, Krox20 and Sox10 at all time points. Expression of N-cadherin was not affected by either stretch or compression. F-actin was down-regulated by tensile stress. CONCLUSIONS: Both tensile and compressive loading down-regulated expression of several important myelin-related Schwann cells genes and thus facilitated demyelination. Tensile stress meanwhile promoted secretion of BDNF by Schwann cells within 24 h, which may contribute to maintenance and repair of damaged axons. These effects of mechanical stress might have been mediated by the actin cytoskeleton.

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