A novel nano-sized bioactive glass stimulates osteogenesis via the MAPK pathway

Abstract

The aims of this study were to compare the osteogenic effects of a novel nano-sized bioactive glass (BG) and a traditional micron-sized BG, and to verify whether mitogen-activated protein kinases (MAPKs) are involved and play a part in BG’s osteoblast gene activation. It was found that the effect of a nano-sized BG on MAPK phosphorylation is better than the traditional 45S5 BG. We prepared extractions of the novel nano-sized 58S BG and traditional 45S5 BG and compared their effect on osteoblast-like cells’ (MG-63 cell) proliferation, osteogenic gene and protein expressions, matrix mineralization and MAPK activation. We further investigated the signal transducing effect of the MAPK pathway on the BG’s osteogenic gene activation. Our results showed that nano-58S extraction enhanced the MG-63 cells’ proliferation and osteogenic gene expressions of alkaline phosphatase (ALP), collagen type I (Col I), Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). The results of ELISA showed more Col I and OCN protein production in the BG groups than in the control group. Greater mineralized nodule formation was found in the nano-58S BG group using alizarin red S staining. We also found that nano-58S and 45S5 BG activated MAPKs, specifically the ERK and p38 pathways, using western blotting. After blocking the ERK or p38 pathway, real-time PCR showed the osteogenic gene activation induced by the BG extractions was inhibited. Blocking the ERK pathway induced a more obvious inhibitory effect on the genes’ normal expression and activation. The significance of this study is that we found that the ERK and p38 MAPK pathways are involved and play an important part in BG’s osteogenic gene activation. The effect of the nano-sized BG on MAPK phosphorylation, osteogenic gene activation, and osteoblast differentiation and mineralization is better than the traditional 45S5 BG.