The role of integrin-linked kinase/β-catenin pathway in the enhanced MG63 differentiation by micro/nano-textured topography

Micro/nano-texturing is a promising approach to produce biomaterials with better tissue integration properties, but the underlying mechanisms are only partially understood. We propose that the integrin-linked kinase (ILK)/β-catenin pathway may play a role in mediating the signals of topographical cues to cells. To confirm the hypothesis, human MG63 osteoblasts are cultured on the micro/nano-textured topographies (MNTs) to assess the cell differentiation in terms of collagen secretion, extracellular matrix mineralization, and osteogenesis-related gene expression. The expression of β-catenin, ILK and integrin β1 and β3 is assayed by real-time polymerase chain reaction and the protein levels of β-catenin, phosphorylated glycogen synthase kinase 3β (p-GSK3β) and ILK are determined by western blot. The ILK silenced MG63 induced by small interfering RNA is cultured on the samples and the cell functions and the levels of β-catenin, GSK3β and p-GSK3β are determined. The results show that the MNTs enhance MG63 differentiation and it is related to the higher expression of integrin β1 and β3 and ILK, which activate the β-catenin signaling by initiating β-catenin expression and inhibiting its degradation by phosphorylating GSK3β. ILK silencing attenuates the β-catenin signaling activation and the enhanced MG63 differentiation by the MNTs. Our results explicitly demonstrate the role of the ILK/β-catenin pathway in mediating the signals from topographical cues to osteoblasts to tailor differentiation and provide new target points for biomaterials modification and biofunctionalization to attain better clinical performance.