Liu Yanchang, Cheng Wendan, Zhao Yao, Gao Liang, Chang Yongyun, Tong Zhicheng, Li Huiwu, Jing Juehua
Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, China.
Sino Euro Orthopaedics Network, Berlin, Germany.
Front Bioeng Biotechnol. 2021 Nov 15;9:735949. doi: 10.3389/fbioe.2021.735949. eCollection 2021.
Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.
骨髓间充质干细胞(BMSCs)在骨形成中起关键作用,并且对外部机械刺激极为敏感。机械信号可调节钛相关假体表面细胞的生物学行为,并诱导BMSCs发生成骨分化,这有利于宿主骨与假体的整合。但其机制仍不清楚。在本研究中,将种植在TiO纳米管表面的BMSCs施加循环机械应力,并探究相关机制。碱性磷酸酶染色、实时PCR和蛋白质印迹结果表明,循环机械应力可通过Wnt/β-连环蛋白调节TiO纳米管表面BMSCs中成骨分化标志物的表达水平。作为组蛋白乙酰转移酶家族的重要成员,GCN5在接收机械信号方面发挥调节作用。染色质免疫沉淀分析结果表明,GCN5可激活Wnt启动子区域。因此,我们得出结论,在循环机械应力刺激下,TiO纳米管表面BMSCs的成骨分化能力增强,且GCN5通过Wnt/β-连环蛋白介导这一过程。