Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Yanchang Liu; Wendan Cheng; Yao Zhao; Liang Gao; Yongyun Chang; Zhicheng Tong; Huiwu Li; Juehua Jing

doi:10.3389/fbioe.2021.735949

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO₂ Nanotubes Through GCN5 and Wnt/β-Catenin

Front Bioeng Biotechnol. 2021 Nov 15:9:735949. doi: 10.3389/fbioe.2021.735949. eCollection 2021.

Authors

Yanchang Liu¹, Wendan Cheng¹, Yao Zhao¹, Liang Gao², Yongyun Chang³, Zhicheng Tong³, Huiwu Li³, Juehua Jing¹

Affiliations

¹ Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei, China.
² Sino Euro Orthopaedics Network, Berlin, Germany.
³ Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

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 TiO₂ 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 TiO₂ 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 TiO₂ nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

Keywords: GCN5 HAT; TiO2 nanotube; Wnt/β-catenin signaling pathway; bone marrow stromal cells; osteogenic differentiation.