炎性微环境中糖原合成酶激酶-3β对颌骨来源骨髓间充质干细胞成骨分化影响研究

Influence of glycogen synthase kinase-3β on osteogenesis of jaw bone marrow mesenchymal stem cells in inflammatory microenvironment

目的探讨炎性微环境中糖原合成酶激酶-3β(GSK-3β)对颌骨来源间充质干细胞(JBMMSCs)成骨分化的影响。方法应用慢病毒(sh RNA)转染技术在JBMMSCs中敲减GSK-3β表达,利用白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α模拟炎症微环境。成骨诱导后利用Western Blot检测成骨相关蛋白表达,茜素红染色检测成骨效率。结果敲减GSK-3β表达可增强JBMMSCs成骨诱导后的成骨相关蛋白表达,成骨效率增强。炎症微环境可显著下调正常JBMMSCs成骨诱导后的成骨相关蛋白表达,成骨效率明显降低,而对敲减GSK-3β表达的JBMMSCs成骨诱导后的成骨相关蛋白表达下调较弱,成骨效率降低较轻。结论抑制GSK-3β既可促进JBMMSCs的成骨作用,又可减轻炎性微环境对JBMMSCs成骨的不良影响,为提高炎症状态下JBMMSCs促进组织再生提供了新的治疗靶点。

Objective To discuss the influence of glycogen synthase kinase-3β （GSK-3β ） on osteogenesis of jaw bone marrow mesenchymal stem cells（JBMMSCs） in inflammatory mieroenvironment. Methods Use shRNA to knock down the expression of GSK-3β in JBMMSCs. IL-1β and TNF-α were used to mimic inflammatory microenvironment. After osteogenesis, Western Blot was used to detect osteogenesis-related protein expression and Alizarin Staining was used to detect the efficiency of osteogenesis in different groups. Results Expression of osteogenesis-related protein and effi- ciency of osteogenesis was highly up-regulated after knocking-down of GSK-3β in JBMMSCs. Inflammatory microenvi- ronment could significantly down-regulate the expression of osteogenesis-related protein and efficiency of osteogenesis in ordinary JBMMSCs, while knocking-down GSK-3β could attenuate this effect. Conclusion Knocking-down of GSK-3 β in JBMMSCs can both increase the efficiency of osteogenesis and resist the adverse effect of inflammatory mi- croenvironment on osteogenesis, thus GSK-3βis a potential target for improving the regeneration in inflammatory micro- environment.