Apolipoprotein E facilitates titanium implant osseointegration by regulating osteogenesis-lipogenesis balance

Apolipoprotein E (ApoE), a protein closely related to various metabolic diseases, is recently considered to play an essential role in bone metabolism. However, the effect and mechanism of ApoE on implant osseointegration have not been clarified. This study aims to investigate the influence of additional ApoE supplementation in regulating the osteogenesis-lipogenesis balance on bone marrow mesenchymal stem cells (BMMSCs) cultured on titanium surface, and the effect of ApoE on the osseointegration of titanium implants. In vivo, the bone volume/total volume (BV/TV) and the bone-implant contact (BIC) significantly elevated in the exogenous supplement of ApoE group, compared with the Normal group. Meanwhile, the adipocyte area proportion around the implant dramatically decreased after 4-week healing. In vitro, the additional ApoE substantially drove the osteogenic differentiation of BMMSCs cultured on the titanium surface and inhibit their lipogenic differentiation as well as lipid droplet accumulation. These results suggest that ApoE, by mediating the differentiation of stem cells on the surface of titanium with this macromolecular protein, is deeply involved in facilitating titanium implant osseointegration, which reveals the potential mechanism and proposes a promising solution for further improving the osseointegration of titanium implants.