Magnetic-Field-Assisted Cellular Osteogenic Differentiation on Magnetic Zinc Ferrite Coatings via MEK/ERK Signaling Pathways

Abstract

Combining an external stimulus and stimuli-responsive biomaterials can regulate cellular behaviors. In this paper, a magneto-responsive zinc ferrite (ZnFe2O4) coating was designed to gain insight into the preosteoblasts behaviors and osteogenic differentiation mechanism under a static magnetic field (SMF). ZnFe2O4 coatings with distinct magnetization (low, medium, and high magnetizations) were prepared by being annealed at different temperatures. Cellular biology experiments indicated that all ZnFe2O4 coatings with the assistance of SMF could promote the early proliferation (3 days) and osteogenic differentiation of MC3T3-E1 cells. Among different ZnFe2O4 samples, low and medium magnetization of ZnFe2O4 showed a higher osteogenesis-related gene expression (Runx2, Col-I, OCN) than that of high magnetization ZnFe2O4 under SMF, while cellular adhesion and proliferation cultured on different ZnFe2O4 samples presented insignificant differences. Molecular biology tests showed that the combination of ferromagnetic ZnFe2O4 and SMF could significantly improve the expression level of α2β1 integrin and p-ERK. However, the addition of the inhibitor U0126 sharply reduced the expression level of p-ERK, which indicated that α2β1 integrin-mediated MEK/ERK signaling pathways play a key role in SMF-assisted cellular osteogenic differentiation over ZnFe2O4 coatings. This work provides an attractive strategy to enhance cellular osteogenic differentiation in a remote-control way, which exhibited enormous potential in the field of bone tissue repair and regeneration.