Senescent Dendritic Cells Affect Osteogenesis By Apoe/Mapk Axis

Our research is dedicated to exploring the regulatory functions of senescent dendritic cells on osteogenesis and their mechanisms. Initially, we established bone defect models in both young and senescent mice to compare their osteogenic capacities and the chemotactic abilities of dendritic cells(DCs). Subsequently, we induced senescence in DCs using D-gal. We then conducted in vitro coculture experiments with MC3T3-E1s to compare their osteogenic differentiation capabilities. Finally, we employed the mechanisms underlying the impaired osteogenic function regulated by senescent DCs through Western blot experiments. We utilized the APOE-/- mice to verify the impact of APOE protein on osteogenesis. In vivo and in vitro experiments have demonstrated that senescent dendritic cells(DCs) inhibit the osteogenic differentiation of MC3T3-E1s and affect the osteogenic capacity of mice. Proteomics results indicate that senescent DCs downregulate the secretion of ApoE protein. Further investigation of ApoE protein reveals that DCs can promote the expression of the MAPK signaling pathway via ApoE. However, the decreased secretion of ApoE by senescent DCs leads to reduced activation of the MAPK pathway. When ApoE protein is supplemented to the supernatant of senescent DCs, osteogenic function and pathway expression are restored. Additionally, in animal experiments, APOE-/- mice exhibit impaired osteogenic capacity. The secretion of ApoE protein by senescent dendritic cells may offer a novel strategy for bone immunotherapy. In clinical treatment, this could provide a new therapeutic target for addressing poor osseointegration of dental implants in elderly patients.