Ma Chao, Wang Jingxian, Fan Longkun
Department of Oral and Maxillofacial Surgery, Cangzhou Central Hospital of Hebei Province, Cangzhou, China.
J Recept Signal Transduct Res. 2019 Aug;39(4):321-330. doi: 10.1080/10799893.2019.1669054. Epub 2019 Oct 1.
Although bone mesenchymal stem cells (BMSCs) have been used for the treatment of oral and maxillofacial defects, the survival rate and limited proliferation reduces the therapeutic efficiency of BMSC. The aim of our study is to explore the role of miR-31 in regulating survival, proliferation, and migration of BMSC . LPS was used to induce BMSC damage and then miR-31 was used to incubate with BMSC. Subsequently, BMSC proliferation, survival, and migration were determined via ELISA, qPCR, western blots, and immunofluorescence. The expression of miR-31 was downregulated in response to LPS stress. Interestingly, supplementation of miR-31 could reverse the survival, proliferation and migration of BMSC under LPS. Mechanically, miR-31 treatment inhibited the activation of caspase, and thus promoted BMSC survival. Besides, miR-31 upregulated the genes related to cell proliferation, an effect that was followed by an increase in the levels of migratory factors. Further, we found that miR-31 treatment activated the CXCR4/Akt pathway and blockade of CXCR4/Akt could abolish the beneficial effects of miR-31 on BMSC proliferation, survival, and migration. miR-31 could increase the therapeutic efficiency of BMSC via the CXCR4/Akt pathway.
尽管骨间充质干细胞(BMSCs)已被用于治疗口腔颌面部缺损,但生存率和有限的增殖能力降低了BMSC的治疗效果。我们研究的目的是探讨miR-31在调节BMSC存活、增殖和迁移中的作用。使用脂多糖(LPS)诱导BMSC损伤,然后用miR-31与BMSC共同孵育。随后,通过酶联免疫吸附测定(ELISA)、定量聚合酶链反应(qPCR)、蛋白质免疫印迹法和免疫荧光法测定BMSC的增殖、存活和迁移情况。在LPS应激下,miR-31的表达下调。有趣的是,补充miR-31可以逆转LPS作用下BMSC的存活、增殖和迁移。从机制上讲,miR-31处理抑制了半胱天冬酶的激活,从而促进了BMSC的存活。此外,miR-31上调了与细胞增殖相关的基因,随后迁移因子水平增加。进一步地,我们发现miR-31处理激活了CXCR4/Akt通路,阻断CXCR4/Akt可以消除miR-31对BMSC增殖、存活和迁移的有益作用。miR-31可以通过CXCR4/Akt通路提高BMSC的治疗效果。