Titanium ion inhibits osteogenic ability of osteoblasts by up-regulating osteoblast Agt gene via macrophages

The pathological mechanism of poor osseointegration of implants caused by aseptic loosening of implants is unclear. This study investigated the changes in implant osseointegration induced by titanium ions and explored the relationship between titanium implants, immune cells and osseointegration and the underlying mechanism of aseptic loosening of titanium implants. In vitro, mouse osteoblasts and mouse macrophages were co-cultured in a titanium ion environment that did not affect osteogenic activity. The results showed that the presence of macrophages in this titanium ion environment caused a decrease in osteogenic capacity. In addition, titanium ions lead to M1 polarization of macrophages and the production of inflammatory mediators, the inflammatory response can affect the ability of osteoblasts. Through transcriptome sequencing analysis of osteoblasts, it was found that the angiotensinogen (Agt) was up-regulated in osteoblasts added to the titanium ion group and knockdown or overexpression of Agt could change the effect of titanium ions on osteoblasts through macrophages. These results indicate that the application of gene Agt may provide new ideas for solving aseptic loosening of implants.