Role of p53 mediated miR-23a/CXCL12 pathway in osteogenic differentiation of bone mesenchymal stem cells on nanostructured titanium surfaces

Abstract

Titanium surface modification is widely established and has been proven to improve the osseointegration, but the molecular mechanism remains to be fully elucidated. MicroRNAs serve vital roles in the process of regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In this study, we report that miR-23a was significantly down-regulated in the osteogenic differentiation process of BMSCs on nanostructured titanium surfaces. Elevated miR-23a inhibited osteogenic differentiation of BMSCs, and decreased miR-23a enhanced this process. In addition, we also observed that CXCL12 was a direct target of miR-23a. Knockdown of CXCL12 inhibited nanotube Ti induced-osteogenic differentiation of BMSCs, similar to the effect of upregulation of miR-23a. Finally, p53 was decreased and it regulated miR-23a/CXCL12 axis during nanotube Ti induced-osteogenic differentiation of BMSCs. Therefore, our findings suggest that by targeting CXCL12, miR-23a serves a vital role in osteogenic differentiation of BMSCs cultured on nanostructured titanium surfaces, which may provide novel clinical treatments for osseointegration.

Keywords

• p53
• Bone marrow-derived mesenchymal stem cells
• miR-23a
• CXCL12
• Osteogenic differentiation
• Nanostructured titanium surfaces