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

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

doi:10.3389/fbioe.2021.735949

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.

Highlights

In the treatment of orthopedic diseases, the integration relationship between the implant prosthesis and the host bone has always been the main factor affecting the therapeutic effect and the life of the implant
These results further validate our previous research findings (Chang et al, 2019). These indicated that rat Bone marrow mesenchymal stem cells (BMSCs) are sensitive to external mechanical signal stimulation, and the elastic deformation caused by cyclic mechanical strain on titanium specimen can promote the osteogenic differentiation of BMSCs
In the application of internal implants, whether BMSCs on the surface of titanium prosthesis can differentiate into osteoblasts is one of the most critical issues determining the osseointegration effect (Wu et al, 2020)

Summary

Introduction

In the treatment of orthopedic diseases, the integration relationship between the implant prosthesis and the host bone has always been the main factor affecting the therapeutic effect and the life of the implant. The integration of the implant prosthesis and the host bone on the interface and the promotion of host bone regeneration have become a momentous indicator for evaluating prostheses performance. The nature of the interaction between the joint prosthesis and host bone interface is the process of bone formation and resorption (Lepri et al, 2016). Bone mesenchymal stem cells (BMSCs) play an important role in bone formation. A recent study showed that the osteogenic differentiation ability of mesenchymal stem cells was enhanced on the surface of high-hardness titanium-related substrates (Tian et al, 2019)

Methods

Results

Conclusion