Involvement of N-cadherin/β-catenin interaction in the micro/nanotopography induced indirect mechanotransduction

Topographical modification at micro- and nanoscale is widely applied to enhance the tissue integration properties of biomaterials, but the underlying molecular mechanism is poorly understood. The biomaterial topography modulates cell functions via mechanotransduction of direct and indirect. We propose that N-cadherin may play a role in the topographically induced indirect mechanotransduction by regulating the β-catenin signaling. For confirmation, the cell functions, N-cadherin expression and β-catenin signaling activation of osteoblasts on titanium (Ti) surfaces with micro- or/and nanotopography are systemically compared with naive and N-cadherin down-regulating MC3T3-E1 cells. We find that the N-cadherin expression is reversely related to the intracellular β-catenin signaling and the N-cadherin/β-catenin signaling is modulated differentially by the micro- and nanotopography. The nanotopography significantly up-regulates the N-cadherin expression leading to lower β-catenin signaling activity and consequently depressed differentiation, whereas the microtopography down-regulates the N-cadherin expression resulting in enhanced β-catenin signaling and thus osteoblast differentiation. Artificial down-regulation of the N-cadherin expression can significantly up-regulate the β-catenin signaling and consequently enhance the osteoblast differentiation on all the Ti surfaces. The study for the first time clarifies the involvement of the N-cadherin/β-catenin interaction in the micro/nanotopography induced indirect mechanotransduction and provides a potentially new approach for biomaterial modification and biofunctionalization by down-regulating the cell N-cadherin expression to achieve improved clinical performance.